Co-reporter:Yuan Gao, Yi Kuang, Zu-Feng Guo, Zhihong Guo, Isaac J. Krauss and Bing Xu
Journal of the American Chemical Society September 30, 2009 Volume 131(Issue 38) pp:13576-13577
Publication Date(Web):September 4, 2009
DOI:10.1021/ja904411z
By covalently connecting taxol with a motif that is prone to self-assemble, we successfully generate the precursor (5a), the hydrogelator (5b), and hydrogel of a taxol derivative without compromising the cytotoxic activity of the taxol. This approach promises a general method to create nanofibers of therapeutic molecules that have a dual role, as both the delivery vehicle and the drug itself.
Co-reporter:Zhaoqianqi Feng, Huaimin Wang, Xiaoyi Chen, and Bing Xu
Journal of the American Chemical Society November 1, 2017 Volume 139(Issue 43) pp:15377-15377
Publication Date(Web):October 9, 2017
DOI:10.1021/jacs.7b07147
Enzyme-instructed self-assembly (EISA) represents a dynamic continuum of supramolecular nanostructures that selectively inhibits cancer cells via simultaneously targeting multiple hallmark capabilities of cancer, but how to design the small molecules for EISA from the vast molecular space remains an unanswered question. Here we show that the self-assembling ability of small molecules controls the anticancer activity of EISA. Examining the EISA precursor analogues consisting of an N-capped d-tetrapeptide, a phosphotyrosine residue, and a diester or a diamide group, we find that, regardless of the stereochemistry and the regiochemistry of their tetrapeptidic backbones, the anticancer activities of these precursors largely match their self-assembling abilities. Additional mechanistic studies confirm that the assemblies of the small peptide derivatives result in cell death, accompanying significant rearrangement of cytoskeletal proteins and plasma membranes. These results imply that the diester or diamide derivatives of the d-tetrapeptides self-assemble pericellularly, as well as intracellularly, to result in cell death. As the first case to correlate thermodynamic properties (e.g., self-assembling ability) of small molecules with the efficacy of a molecule process against cancer cells, this work provides an important insight for developing a molecular dynamic continuum for potential cancer therapy, as well as understanding the cytotoxicity of pathogenic assemblies.
Co-reporter:Zhaoqianqi Feng, Huaimin Wang, Rong Zhou, Jie Li, and Bing Xu
Journal of the American Chemical Society March 22, 2017 Volume 139(Issue 11) pp:3950-3950
Publication Date(Web):March 3, 2017
DOI:10.1021/jacs.7b00070
Cancer cells differ from normal cells in both gain of functions (i.e., upregulation) and loss of functions (i.e., downregulation). While it is common to suppress gain of function for chemotherapy, it remains challenging to target downregulation in cancer cells. Here we show the combination of enzyme-instructed assembly and disassembly to target downregulation in cancer cells by designing peptidic precursors as the substrates of both carboxylesterases (CESs) and alkaline phosphatases (ALPs). The precursors turn into self-assembling molecules to form nanofibrils upon dephosphorylation by ALP, but CES-catalyzed cleavage of the ester bond on the molecules results in disassembly of the nanofibrils. The precursors selectively inhibit the cancer cells that downregulate CES (e.g., OVSAHO) but are innocuous to a hepatocyte that overexpresses CES (HepG2), while the two cell lines exhibit comparable ALP activities. This work illustrates a potential approach for the development of chemotherapy via targeting downregulation (or loss of functions) in cancer cells.
Co-reporter:Yuan Gao, Yi Kuang, Xuewen Du, Jie Zhou, Preethi Chandran, Ferenc Horkay, and Bing Xu
Langmuir December 10, 2013 Volume 29(Issue 49) pp:15191-15200
Publication Date(Web):November 22, 2013
DOI:10.1021/la403457c
Self-assembly of small molecules, as a more common phenomenon than one previously thought, can be either beneficial or detrimental to cells. Despite its profound biological implications, how the self-assembly of small molecules behave in a cellular environment is largely unknown and barely explored. This work studies four fluorescent molecules that consist of the same peptidic backbone (e.g., Phe–Phe–Lys) and enzyme trigger (e.g., a phosphotyrosine residue), but bear different fluorophores on the side chain of the lysine residue of the peptidic motif. These molecules, however, exhibit a different ability of self-assembly before and after enzymatic transformation (e.g., dephosphorylation). Fluorescent imaging reveals that self-assembly directly affects the distribution of these small molecules in a cellular environment. Moreover, cell viability tests suggest that the states and the locations of the molecular assemblies in the cellular environment control the phenotypes of the cells. For example, the molecular nanofibers of one of the small molecules apparently stabilize actin filaments and alleviate the insult of an F-actin toxin (e.g., latrunculin A). Combining fluorescent imaging and enzyme-instructed self-assembly of small peptidic molecules, this work demonstrates self-assembly as a key factor for dictating the spatial distribution of small molecules in a cellular environment. In addition, it illustrates a useful approach, based on enzyme-instructed self-assembly of small molecules, to modulate spatiotemporal profiles of small molecules in a cellular environment, which allows the use of the emergent properties of small molecules to control the fate of cells.
Co-reporter:Huaimin Wang;Zhaoqianqi Feng
Chemical Society Reviews 2017 vol. 46(Issue 9) pp:2421-2436
Publication Date(Web):2017/05/09
DOI:10.1039/C6CS00656F
Self-assembly, the autonomous organization of components to form patterns or structures, is a prevalent process in nature at all scales. Particularly, biological systems offer remarkable examples of diverse structures (as well as building blocks) and processes resulting from self-assembly. The exploration of bioinspired assemblies not only allows for mimicking the structures of living systems, but it also leads to functions for applications in different fields that benefit humans. In the last several decades, efforts on understanding and controlling self-assembly of small molecules have produced a large library of candidates for developing the biomedical applications of assemblies of small molecules. Moreover, recent findings in biology have provided new insights on the assemblies of small molecules to modulate essential cellular processes (such as apoptosis). These observations indicate that the self-assembly of small molecules, as multifaceted entities and processes to interact with multiple proteins, can have profound biological impacts on cells. In this review, we illustrate that the generation of assemblies of small molecules in cell milieu with their interactions with multiple cellular proteins for regulating cellular processes can result in primary phenotypes, thus providing a fundamentally new molecular approach for controlling cell behavior. By discussing the correlation between molecular assemblies in nature and the assemblies of small molecules in cell milieu, illustrating the functions of the assemblies of small molecules, and summarizing some guiding principles, we hope this review will stimulate more molecular scientists to explore the bioinspired self-assembly of small molecules in cell milieu.
Co-reporter:Jie Li;Junfeng Shi;Jamie E. Medina;Jie Zhou;Xuewen Du;Huaimin Wang;Cuihong Yang;Jianfeng Liu;Zhimou Yang;Daniela M. Dinulescu
Advanced Healthcare Materials 2017 Volume 6(Issue 15) pp:
Publication Date(Web):2017/08/01
DOI:10.1002/adhm.201601400
Tight ligand-receptor binding, paradoxically, is a major root of drug resistance in cancer chemotherapy. To address this problem, instead of using conventional inhibitors or ligands, this paper focuses on the development of a novel process—enzyme-instructed self-assembly (EISA)—to kill cancer cells selectively. Here it is demonstrated that EISA as an intracellular process to generate nanofibrils of short peptides for selectively inhibiting cancer cell proliferation, including drug resistant ones. As the process that turns the non-self-assembling precursors into the self-assembling peptides upon the catalysis of carboxylesterases (CES), EISA occurs intracellularly to selectively inhibit a range of cancer cells that exhibit relatively high CES activities. More importantly, EISA inhibits drug resistant cancer cells (e.g., triple negative breast cancer cells (HCC1937) and platinum-resistant ovarian cells (SKOV3, A2780cis)). With the IC50 values of 28–80 and 25–44 µg mL−1 of l- and d-dipeptide precursors against cancer cells, respectively, EISA is innocuous to normal cells. Moreover, using coculture of cancer and normal cells, the selectivity of EISA is validated against cancer cells. Besides revealing that intracellular EISA cause apoptosis or necroptosis to kill the cancer cells, this work illustrates a new approach to amplify the enzymatic difference between cancer and normal cells and to expand the pool of drug candidates for potentially overcoming drug resistance in cancer therapy.
Co-reporter:Jie Zhou, Jie Li, Xuewen Du, Bing Xu
Biomaterials 2017 Volume 129(Volume 129) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.biomaterials.2017.03.014
This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness. In this review, besides elaborating on the merits of supramolecular biofunctional materials (mainly in the form of hydrogels and/or nanoscale assemblies) resulting from noncovalent interactions, we also discuss the advantages of small peptides as a prevalent molecular platform to generate a wide range of supramolecular biofunctional materials for the applications in drug delivery, tissue engineering, immunology, cancer therapy, fluorescent imaging, and stem cell regulation. This review aims to provide a brief synopsis of recent achievements at the intersection of supramolecular chemistry and biomedical science in hope of contributing to the multidisciplinary research on supramolecular biofunctional materials for a wide range of applications. We envision that supramolecular biofunctional materials will contribute to the development of new therapies that will ultimately lead to a paradigm shift for developing next generation biomaterials for medicine.
Co-reporter:Natsuko Yamagata;Xiaoyi Chen;Jie Zhou;Jie Li;Xuewen Du
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 27) pp:5689-5692
Publication Date(Web):2017/07/12
DOI:10.1039/C7OB01074E
Here we show the first example of an immunoreceptor tyrosine-based inhibitory motif (ITIM), LYYYYL, as well as its enantiomeric or retro-inverso peptide, to self-assemble in water via enzyme-instructed self-assembly. Upon enzymatic dephosphorylation, the phosphohexapeptides become hexapeptides, which self-assemble in water to result in supramolecular hydrogels. This work illustrates a new approach to design bioinspired soft materials from a less explored, but important pool of immunomodulatory peptides.
Co-reporter:Honggang Cui
Chemical Society Reviews 2017 vol. 46(Issue 21) pp:6430-6432
Publication Date(Web):2017/10/30
DOI:10.1039/C7CS90102J
A graphical abstract is available for this content
Co-reporter:Dr. Huaimin Wang;Dr. Junfeng Shi;Zhaoqianqi Feng;Dr. Rong Zhou;Shiyu Wang; Avital A. Rodal; Dr. Bing Xu
Angewandte Chemie 2017 Volume 129(Issue 51) pp:16515-16519
Publication Date(Web):2017/12/18
DOI:10.1002/ange.201710269
AbstractHigher-order assemblies of proteins, with a structural and dynamic continuum, is an important concept in biology, but these insights have yet to be applied in designing biomaterials. Dynamic assemblies of supramolecular phosphoglycopeptides (sPGPs) transform a 2D cell sheet into 3D cell spheroids. A ligand–receptor interaction between a glycopeptide and a phosphopeptide produces sPGPs that form nanoparticles, which transform into nanofibrils upon partial enzymatic dephosphorylation. The assemblies form dynamically and hierarchically in situ on the cell surface, and interact with the extracellular matrix molecules and effectively abolish contact inhibition of locomotion (CIL) of the cells. Integrating molecular recognition, catalysis, and assembly, these active assemblies act as a dynamic continuum to disrupt CIL, thus illustrating a new kind of biomaterial for regulating cell behavior.
Co-reporter:Ning Zhou;Dr. Xiaoyan Cao;Xuewen Du;Dr. Huaimin Wang;Dr. Ming Wang;Dr. Shuang Liu;Khang Nguyen; Klaus Schmidt-Rohr; Qiaobing Xu; Gaolin Liang; Bing Xu
Angewandte Chemie 2017 Volume 129(Issue 10) pp:2667-2671
Publication Date(Web):2017/03/01
DOI:10.1002/ange.201611479
AbstractHydrogels consisting of carboxylic acid groups and N-isopropylacrylamide as pendants on their polymeric network usually exhibit volume expansion upon deprotonation or volume contraction when being heated. Demonstrated here is an anti-intuitive case of a hydrogel containing multiple carboxylic acid groups at each crosslinking point in the polymeric network, which shrinks upon increasing pH from 1 to 7 at 37 °C or expands upon heating from 25 to 37 °C at pH 1. The unexpected volume change originates from the high percentage of the crosslinker in the polymers, as detected by solid-state 13C NMR spectroscopy. In addition, the volume changes are thermally reversible. As the first example of the use of functional hyper-crosslinkers to control the pH and thermal responses of nanogels, this work illustrates a new way to design soft materials with unusual behaviors.
Co-reporter:Dr. Huaimin Wang;Dr. Junfeng Shi;Zhaoqianqi Feng;Dr. Rong Zhou;Shiyu Wang; Avital A. Rodal; Dr. Bing Xu
Angewandte Chemie International Edition 2017 Volume 56(Issue 51) pp:16297-16301
Publication Date(Web):2017/12/18
DOI:10.1002/anie.201710269
AbstractHigher-order assemblies of proteins, with a structural and dynamic continuum, is an important concept in biology, but these insights have yet to be applied in designing biomaterials. Dynamic assemblies of supramolecular phosphoglycopeptides (sPGPs) transform a 2D cell sheet into 3D cell spheroids. A ligand–receptor interaction between a glycopeptide and a phosphopeptide produces sPGPs that form nanoparticles, which transform into nanofibrils upon partial enzymatic dephosphorylation. The assemblies form dynamically and hierarchically in situ on the cell surface, and interact with the extracellular matrix molecules and effectively abolish contact inhibition of locomotion (CIL) of the cells. Integrating molecular recognition, catalysis, and assembly, these active assemblies act as a dynamic continuum to disrupt CIL, thus illustrating a new kind of biomaterial for regulating cell behavior.
Co-reporter:Dr. Huaimin Wang;Zhaoqianqi Feng;Dr. Alvin Lu;Yujie Jiang; Dr. Hao Wu; Dr. Bing Xu
Angewandte Chemie International Edition 2017 Volume 56(Issue 26) pp:7579-7583
Publication Date(Web):2017/06/19
DOI:10.1002/anie.201702783
AbstractBased on the recent near-atomic structures of the PYRIN domain of ASC in the protein filament of inflammasomes and the observation that the active form of vitamin B6 (pyridoxal phosphate, P5P) modulates the self-assembly of ASC, we rationally designed an N-terminal capped nonapeptide (Nap-FFKKFKLKL, 1) to form supramolecular nanofibers consisting of α-helix. The addition of P5P to the solution of 1 results in a hydrogel almost instantly (about 4 seconds). Several other endogenous small molecules (for example, pyridoxal, folinic acid, ATP, and AMP) also convert the solution of 1 into a hydrogel. As the demonstration of correlating assemblies of peptides and the relevant protein epitopes, this work illustrates a bioinspired approach to develop supramolecular structures modulated by endogenous small molecules.
Co-reporter:Huaimin Wang, Zhaoqianqi Feng, Dongdong Wu, Keith J. Fritzsching, Mike Rigney, Jie Zhou, Yujie Jiang, Klaus Schmidt-Rohr, and Bing Xu
Journal of the American Chemical Society 2016 Volume 138(Issue 34) pp:10758-10761
Publication Date(Web):August 16, 2016
DOI:10.1021/jacs.6b06075
We report that phosphotyrosine–cholesterol conjugates effectively and selectively kill cancer cells, including platinum-resistant ovarian cancer cells. The conjugate increases the degree of noncovalent oligomerization upon enzymatic dephosphorylation in aqueous buffer. This enzymatic conversion also results in the assembly of the cholesterol conjugates inside and outside cells and leads to cell death. Preliminary mechanistic studies suggest that the formed assemblies of the conjugates not only interact with actin filaments and microtubules but also affect lipid rafts. As the first report of multifaceted supramolecular assemblies of cholesterol conjugates against cancer cells, this work illustrates the integration of enzyme catalysis and self-assembly of essential biological small molecules on and inside cancer cells as a promising strategy for developing multifunctional therapeutics to treat drug-resistant cancers.
Co-reporter:Jie Li, Xuewen Du, Saqib Hashim, Adrianna Shy, and Bing Xu
Journal of the American Chemical Society 2016 Volume 139(Issue 1) pp:71-74
Publication Date(Web):December 20, 2016
DOI:10.1021/jacs.6b11512
Isolated short peptides usually are unable to maintain their original secondary structures due to the lack of the restriction from proteins. Here we show that two complementary pentapeptides from a β-sheet motif of a protein, being connected to an aromatic motif (i.e., pyrene) at their C-terminal, self-assemble to form β-sheet like structures upon mixing. Besides enabling the self-assembly to result in supramolecular hydrogels upon mixing, aromatic–aromatic interactions promote the pentapeptides transform from α-helix to β-sheet conformation. As the first example of using aromatic–aromatic interactions to mimic the conformational restriction in a protein, this work illustrates a bioinspired way to generate peptide nanofibers with predefined secondary structures of the peptides by a rational design using protein structures as the blueprint.
Co-reporter:Huaimin WangZhaoqianqi Feng, Youzhi Wang, Rong Zhou, Zhimou Yang, Bing Xu
Journal of the American Chemical Society 2016 Volume 138(Issue 49) pp:16046-16055
Publication Date(Web):November 14, 2016
DOI:10.1021/jacs.6b09783
Targeting organelles by modulating the redox potential of mitochondria is a promising approach to kill cancer cells that minimizes acquired drug resistance. However, it lacks selectivity because mitochondria perform essential functions for (almost) all cells. We show that enzyme-instructed self-assembly (EISA), a bioinspired molecular process, selectively generates the assemblies of redox modulators (e.g., triphenyl phosphinium (TPP)) in the pericellular space of cancer cells for uptake, which allows selectively targeting the mitochondria of cancer cells. The attachment of TPP to a pair of enantiomeric, phosphorylated tetrapeptides produces the precursors (L-1P or D-1P) that form oligomers. Upon dephosphorylation catalyzed by ectophosphatases (e.g., alkaline phosphatase (ALP)) overexpressed on cancer cells (e.g., Saos2), the oligomers self-assemble to form nanoscale assemblies only on the surface of the cancer cells. The cancer cells thus uptake these assemblies of TPP via endocytosis, mainly via a caveolae/raft-dependent pathway. Inside the cells, the assemblies of TPP-peptide conjugates escape from the lysosome, induce dysfunction of mitochondria to release cytochrome c, and result in cell death, while the controls (i.e., omitting TPP motif, inhibiting ALP, or removing phosphate trigger) hardly kill the Saos2 cells. Most importantly, the repeated stimulation of the cancers by the precursors, unexpectedly, sensitizes the cancer cells to the precursors. As the first example of the integration of subcellular targeting with cell targeting, this study validates the spatial control of the assemblies of nonspecific cytotoxic agents by EISA as a promising molecular process for selectively killing cancer cells without inducing acquired drug resistance.
Co-reporter:Richard Haburcak, Junfeng Shi, Xuewen Du, Dan Yuan, and Bing Xu
Journal of the American Chemical Society 2016 Volume 138(Issue 47) pp:15397-15404
Publication Date(Web):October 31, 2016
DOI:10.1021/jacs.6b07677
The concurrence of enzymatic reaction and ligand–receptor interactions is common for proteins, but rare for small molecules and has yet to be explored. Here we show that ligand–receptor interaction modulates the morphology of molecular assemblies formed by enzyme-instructed assembly of small molecules. While the absence of ligand–receptor interaction allows enzymatic dephosphorylation of a precursor to generate the hydrogelator that self-assembles to form long nanofibers, the presence of the ligand–receptor interaction biases the pathway to form precipitous aggregates containing short nanofibers. While the hydrogelators self-assemble to form nanofibers or nanoribbons that are unable to bind with the ligand (i.e., vancomycin), the addition of surfactant breaks up the assemblies to restore the ligand–receptor interaction. In addition, an excess amount of the ligands can disrupt the nanofibers and result in the precipitates. As the first example of the use of ligand–receptor interaction to modulate the kinetics of enzymatic self-assembly, this work not only provides a solution to evaluate the interaction between aggregates and target molecules but also offers new insight for understanding the emergent behavior of sophisticated molecular systems having multiple and parallel processes.
Co-reporter:Jie Zhou; Xuewen Du; Natsuko Yamagata
Journal of the American Chemical Society 2016 Volume 138(Issue 11) pp:3813-3823
Publication Date(Web):March 11, 2016
DOI:10.1021/jacs.5b13541
Selective inhibition of cancer cells remains a challenge in chemotherapy. Here we report the molecular and cellular validation of enzyme-instructed self-assembly (EISA) as a multiple step process for selectively killing cancer cells that overexpress alkaline phosphatases (ALPs). We design and synthesize two kinds of d-tetrapeptide containing one or two phosphotyrosine residues and with the N-terminal capped by a naphthyl group. Upon enzymatic dephosphorylation, these d-tetrapeptides turn into self-assembling molecules to form nanofibers in water. Incubating these d-tetrapeptides with several cancer cell lines and one normal cell line, the unphosphorylated d-tetrapeptides are innocuous to all the cell lines, the mono- and diphosphorylated d-tetrapeptides selectively inhibit the cancer cells, but not the normal cell. The monophosphorylated d-tetrapeptides exhibit more potent inhibitory activity than the diphosphorylated d-tetrapeptides do; the cancer cell lines express higher level of ALPs are more susceptible to inhibition by the phosphorylated d-tetrapeptides; the precursors of d-tetrapeptides that possess higher self-assembling abilities exhibit higher inhibitory activities. These results confirm the important role of enzymatic reaction and self-assembly. Using uncompetitive inhibitors of ALPs and fluorescent d-tetrapeptides, we delineate that the enzyme catalyzed dephosphorylation and the self-assembly steps, together, result in the localization of the nanofibers of d-tetrapeptides for killing the cancer cells. We find that the cell death modality likely associates with the cell type and prove the interactions between nanofibers and the death receptors. This work illustrates a paradigm-shifting and biomimetic approach and contributes useful molecular insights for the development of spatiotemporal defined supramolecular processes/assemblies as potential anticancer therapeutics.
Co-reporter:Dan Yuan, Junfeng Shi, Xuewen Du, Yibing Huang, Yuan Gao, Abdulgader A. Baoum and Bing Xu
Journal of Materials Chemistry A 2016 vol. 4(Issue 7) pp:1318-1323
Publication Date(Web):11 Jan 2016
DOI:10.1039/C5TB02346G
Based on the self-assembly capability of the core segment (GNNQQNY) of yeast prion Sup35, we design and synthesise a series of structurally related precursors for the enzymatic formation of hydrogels. We found that, with the catalysis of alkaline phosphatase, the precursor becomes a hydrogelator that self-assembles in water to form nanofibers with an average width less than ten nanometers. Interestingly, the introduction of an amyloid segment into a cytotoxic precursor (N′ffyp: D-1P) is able to abrogate the cytotoxicity of the precursor, making the resulting peptide cell compatible. This work contributes a new insight into the use of enzymes to form cell compatible hydrogels of peptide cross-β spine.
Co-reporter:Zhaoqianqi Feng, Huaimin Wang, Xuewen Du, Junfeng Shi, Jie Li and Bing Xu
Chemical Communications 2016 vol. 52(Issue 37) pp:6332-6335
Publication Date(Web):08 Apr 2016
DOI:10.1039/C6CC02282K
Here we reported the first case in which enhancing self-assembling ability boosts anti-cancer efficacy through a simple and minimal modification of the C-terminus of a D-tripeptide. By only a 2% change of the molecular weight, this facile approach increases the inhibitory activity by over an order of magnitude (IC50 from 431 to 23 μM) towards an osteosarcoma cell line.
Co-reporter:Jie Zhou, Michael O'Keeffe, Gongxian Liao, Fan Zhao, Cox Terhorst, Bing Xu
Tetrahedron 2016 Volume 72(Issue 40) pp:6078-6083
Publication Date(Web):6 October 2016
DOI:10.1016/j.tet.2016.07.057
The medical practice for IBD is solely based on anti-inflammatory drugs, but the outcome is far from ideal. Our long-term research goal is to seek a better clinical outcome by combining the anti-inflammatory therapy with physical mucus layer restoration. As the first step towards that objective, we choose to develop self-assembled hydrogels of de novo glycoconjugates that consist of anti-inflammatory drugs and glycopeptides. By covalently linking peptides (e.g., nap-phe-phe-lys), saccharides (e.g., glucosamine), and an anti-inflammatory drug (i.e., olsalazine), we have demonstrated that the obtained molecules self-assemble in water to form hydrogels composed of 3D networks of the nanofibers under acidic conditions. We also confirmed that the resulting glycoconjugates are cell compatible. However, the preliminary assessment of the efficacy of the hydrogels on the murine model is inconclusive, which warrants further investigation and molecular engineering.
Co-reporter:Jie Zhou;Xuewen Du ;Dr. Bing Xu
Angewandte Chemie 2016 Volume 128( Issue 19) pp:5864-5869
Publication Date(Web):
DOI:10.1002/ange.201600753
Abstract
Besides tight and specific ligand–receptor interactions, the rate regulation of the formation of molecular assemblies is one of fundamental features of cells. But the latter receives little exploration for developing anticancer therapeutics. Here we show that a simple molecular design of the substrates of phosphatases—tailoring the number of phosphates on peptidic substrates—is able to regulate the rate of molecular self-assembly of the enzyme reaction product. Such a rate regulation allows selective inhibition of osteosarcoma cells over hepatocytes, which promises to target cancer cells in a specific organ. Moreover, our result reveals that the direct measurement of the rate of the self-assembly in a cell-based assay provides precise assessment of the cell targeting capability of self-assembly. This work, as the first report establishing rate regulation of a multiple-step process to inhibit cells selectively, illustrates a fundamentally new approach for controlling the fate of cells.
Co-reporter:Jie Zhou;Xuewen Du ;Dr. Bing Xu
Angewandte Chemie International Edition 2016 Volume 55( Issue 19) pp:5770-5775
Publication Date(Web):
DOI:10.1002/anie.201600753
Abstract
Besides tight and specific ligand–receptor interactions, the rate regulation of the formation of molecular assemblies is one of fundamental features of cells. But the latter receives little exploration for developing anticancer therapeutics. Here we show that a simple molecular design of the substrates of phosphatases—tailoring the number of phosphates on peptidic substrates—is able to regulate the rate of molecular self-assembly of the enzyme reaction product. Such a rate regulation allows selective inhibition of osteosarcoma cells over hepatocytes, which promises to target cancer cells in a specific organ. Moreover, our result reveals that the direct measurement of the rate of the self-assembly in a cell-based assay provides precise assessment of the cell targeting capability of self-assembly. This work, as the first report establishing rate regulation of a multiple-step process to inhibit cells selectively, illustrates a fundamentally new approach for controlling the fate of cells.
Co-reporter:Xuewen Du, Jie Zhou, Junfeng Shi, and Bing Xu
Chemical Reviews 2015 Volume 115(Issue 24) pp:13165
Publication Date(Web):December 8, 2015
DOI:10.1021/acs.chemrev.5b00299
In this review we intend to provide a relatively comprehensive summary of the work of supramolecular hydrogelators after 2004 and to put emphasis particularly on the applications of supramolecular hydrogels/hydrogelators as molecular biomaterials. After a brief introduction of methods for generating supramolecular hydrogels, we discuss supramolecular hydrogelators on the basis of their categories, such as small organic molecules, coordination complexes, peptides, nucleobases, and saccharides. Following molecular design, we focus on various potential applications of supramolecular hydrogels as molecular biomaterials, classified by their applications in cell cultures, tissue engineering, cell behavior, imaging, and unique applications of hydrogelators. Particularly, we discuss the applications of supramolecular hydrogelators after they form supramolecular assemblies but prior to reaching the critical gelation concentration because this subject is less explored but may hold equally great promise for helping address fundamental questions about the mechanisms or the consequences of the self-assembly of molecules, including low molecular weight ones. Finally, we provide a perspective on supramolecular hydrogelators. We hope that this review will serve as an updated introduction and reference for researchers who are interested in exploring supramolecular hydrogelators as molecular biomaterials for addressing the societal needs at various frontiers.
Co-reporter:Jie Zhou; Xuewen Du; Jie Li; Natsuko Yamagata
Journal of the American Chemical Society 2015 Volume 137(Issue 32) pp:10040-10043
Publication Date(Web):August 1, 2015
DOI:10.1021/jacs.5b06181
Due to their biostability, d-peptides are emerging as an important molecular platform for biomedical applications. Being proteolytically resistant, d-peptides lack interactions with endogenous transporters and hardly enter cells. Here we show that taurine, a natural amino acid, drastically boosts the cellular uptake of small d-peptides in mammalian cells by >10-fold, from 118 μM (without conjugating taurine) to >1.6 mM (after conjugating taurine). The uptake of a large amount of the ester conjugate of taurine and d-peptide allows intracellular esterase to trigger intracellular self-assembly of the d-peptide derivative, further enhancing their cellular accumulation. The study on the mechanism of the uptake reveals that the conjugates enter cells via both dynamin-dependent endocytosis and macropinocytosis, but likely not relying on taurine transporters. Differing fundamentally from the positively charged cell-penetrating peptides, the biocompatibility, stability, and simplicity of the enzyme-cleavable taurine motif promise new ways to promote the uptake of bioactive molecules for countering the action of efflux pump and contributing to intracellular molecular self-assembly.
Co-reporter:Dan Yuan; Junfeng Shi; Xuewen Du; Ning Zhou
Journal of the American Chemical Society 2015 Volume 137(Issue 32) pp:10092-10095
Publication Date(Web):August 3, 2015
DOI:10.1021/jacs.5b05888
Despite the recent consensus that the oligomers of amyloid peptides or aberrant proteins are cytotoxic species, there is still a need for an effective way to eliminate the oligomers. Based on the fact that normal proteins are more glycosylated than pathogenic proteins, we show that a conjugate of nucleobase, peptide, and saccharide binds to peptides from molecular nanofibrils and accelerates the proteolytic degradation of the molecular nanofibrils. As the first example of the use of supramolecular glycosylation to dissociate molecular nanofibrils and to accelerate the degradation of peptide aggregates, this work illustrates a new method that ultimately may lead to an effective approach for degrading cytotoxic oligomers of peptides or aberrant proteins.
Co-reporter:Junfeng Shi, Xuewen Du, Dan Yuan, Richard Haburcak, Dongdong Wu, Ning Zhou and Bing Xu
Chemical Communications 2015 vol. 51(Issue 23) pp:4899-4901
Publication Date(Web):12 Feb 2015
DOI:10.1039/C4CC10374B
Enzymatic transformation is a fundamental process to control ligand–receptor interactions among proteins for signal transduction in cells. Here we report the first example of enzymatic transformation regulated ligand–receptor interactions of small molecules, in which enzymatic reaction changes the stoichiometry of the ligand–receptor binding from 1:1 to 1:2. We also show that this unique integration of enzymatic transformation and ligand–receptor interactions of small molecules is able to affect the fate of cells.
Co-reporter:Junfeng Shi, Xuewen Du, Dan Yuan, Richard Haburcak, Ning Zhou, and Bing Xu
Bioconjugate Chemistry 2015 Volume 26(Issue 9) pp:1879
Publication Date(Web):August 10, 2015
DOI:10.1021/acs.bioconjchem.5b00356
Insoluble amyloid plagues are likely cytoprotective, but the cellular mechanism remains less known. To model β-amyloid we use a small peptide derivative to generate cytotoxic nanofibrils that cause the death of model neuron cells (i.e., PC12). The use of supramolecular interaction effectively converts the nanofibrils to nanoparticles that are innocuous to cells. This approach also removes the cytotoxicity of the fibrils to other mammalian cells (e.g., HeLa). Preliminary mechanistic study reveals that, in contrast to the fibrils, the particles promote the expression of TNFR2, a cell survival signal, and decrease the expression of TNFR1 and DR5, two extrinsic cell death receptors. As the first use of ligand–receptor interaction to abrogate the cytotoxicity of nanoscale assemblies of small molecules, this work illustrates an effective way to use supramolecular interaction to control the morphology of supramolecular assemblies for modulating their biological activity.
Co-reporter:Jie Zhou and Bing Xu
Bioconjugate Chemistry 2015 Volume 26(Issue 6) pp:987
Publication Date(Web):May 1, 2015
DOI:10.1021/acs.bioconjchem.5b00196
The central dogma of the action of current anticancer drugs is that the drug tightly binds to its molecular target for inhibition. The reliance on tight ligand–receptor binding, however, is also the major root of drug resistance in cancer therapy. In this article, we highlight enzyme-instructed self-assembly (EISA)—the integration of enzymatic transformation and molecular self-assembly—as a multistep process for the development of cancer therapy. Using apoptosis as an example, we illustrate that the combination of enzymatic transformation and self-assembly, in fact, is an inherent feature of apoptosis. After the introduction of EISA of small molecules in the context of supramolecular hydrogelation, we describe several key studies to underscore the promises of EISA for developing cancer therapy. Particularly, we will highlight that EISA allows one to develop approaches to target “undruggable” targets or “untargetable” features of cancer cells and provides the opportunity for simultaneously interacting with multiple targets. We envision that EISA, used separately or in combination with current anticancer therapeutics, will ultimately lead to a paradigm shift for developing anticancer medicine that inhibit multiple hallmark capabilities of cancer.
Co-reporter:Dan Yuan;Xuewen Du;Junfeng Shi;Ning Zhou;Jie Zhou ;Dr. Bing Xu
Angewandte Chemie International Edition 2015 Volume 54( Issue 19) pp:5705-5708
Publication Date(Web):
DOI:10.1002/anie.201412448
Abstract
As a new class of biomaterials, most supramolecular hydrogels formed by small peptides require the attachment of long alkyl chains, multiple aromatic groups, or strong electrostatic interactions. Based on the fact that the most abundant protein assemblies in nature are dimeric, we select short peptide sequences from the interface of a heterodimer of proteins with known crystal structure to conjugate with nucleobases to form nucleopeptides. Being driven mainly by hydrogen bonds, the nucleopeptides self-assemble to form nanofibers, which results in supramolecular hydrogels upon simple mixing of two distinct nucleopeptides in water. Moreover, besides being biocompatible to mammalian cells, the heterodimer of the nucleopeptides exhibit excellent proteolytic resistance against proteinase K. This work illustrates a new and rational approach to create soft biomaterials by a supramolecular hydrogelation triggered by mixing heterodimeric nucleopeptides.
Co-reporter:Dan Yuan;Xuewen Du;Junfeng Shi;Ning Zhou;Jie Zhou ;Dr. Bing Xu
Angewandte Chemie 2015 Volume 127( Issue 19) pp:5797-5800
Publication Date(Web):
DOI:10.1002/ange.201412448
Abstract
As a new class of biomaterials, most supramolecular hydrogels formed by small peptides require the attachment of long alkyl chains, multiple aromatic groups, or strong electrostatic interactions. Based on the fact that the most abundant protein assemblies in nature are dimeric, we select short peptide sequences from the interface of a heterodimer of proteins with known crystal structure to conjugate with nucleobases to form nucleopeptides. Being driven mainly by hydrogen bonds, the nucleopeptides self-assemble to form nanofibers, which results in supramolecular hydrogels upon simple mixing of two distinct nucleopeptides in water. Moreover, besides being biocompatible to mammalian cells, the heterodimer of the nucleopeptides exhibit excellent proteolytic resistance against proteinase K. This work illustrates a new and rational approach to create soft biomaterials by a supramolecular hydrogelation triggered by mixing heterodimeric nucleopeptides.
Co-reporter:Junfeng Shi;Dan Yuan;Richard Haburcak;Qiang Zhang;Dr. Chao Zhao;Dr. Xixiang Zhang;Dr. Bing Xu
Chemistry - A European Journal 2015 Volume 21( Issue 50) pp:18047-18051
Publication Date(Web):
DOI:10.1002/chem.201504087
Abstract
Enzyme-catalyzed dephosphorylation is essential for biomineralization and bone metabolism. Here we report the exploration of using enzymatic reaction to transform biocomposites of phosphopeptides and calcium (or strontium) ions to supramolecular hydrogels as a mimic of enzymatic dissolution of biominerals. 31P NMR shows that strong affinity between the phosphopeptides and alkaline metal ions (e.g., Ca2+ or Sr2+) induces the formation of biocomposites as precipitates. Electron microscopy reveals that the enzymatic reaction regulates the morphological transition from particles to nanofibers. Rheology confirms the formation of a rigid hydrogel. As the first example of enzyme-instructed dissolution of a solid to form supramolecular nanofibers/hydrogels, this work provides an approach to generate soft materials with desired properties, expands the application of supramolecular hydrogelators, and offers insights to control the demineralization of calcified soft tissues.
Co-reporter:Junfeng Shi, Bing Xu
Nano Today 2015 Volume 10(Issue 5) pp:615-630
Publication Date(Web):October 2015
DOI:10.1016/j.nantod.2015.09.001
•Nanoscale assemblies of glycoconjugates promote the proliferation of stem cells.•Selective inhibition of cancer cells by enzyme-instructed self-assembly of d-peptides to form pericellular nanofibrils.•Ligand–receptor interactions catalyze the formation of nanoscale assemblies.•Visualize the nanoscale assemblies of small molecules in cellular environment.•Hydrogel-based assay identifies the target proteins of nanoscale assemblies.Being driven by non-covalent interactions, the formation of functional assemblies (or aggregates) of small molecules at nanoscale is a more common process in water than one would think. While most efforts on self-assembly in cellular environment concentrate on the assemblies of proteins (e.g., microtubules or amyloid fibers), nanoscale assemblies of small molecules are emerging functional entities that exhibit important biological function in cellular environments. This review describes the increasing efforts on the exploration of nanoscale assemblies of small molecules that largely originate from the serendipitous observations in research fields other than nanoscience and technology. Specifically, we describe that nanoscale assemblies of small molecules exhibit unique biological functions in extracellular and intracellular environment, thus inducing various cellular responses, like causing cell death or promoting cell proliferation. We first survey certain common feature of nanoscale molecular assemblies, then discuss several specific examples, such as, nanoscale assemblies of small peptides accumulated in the cells for selectively inhibiting cancer cells via promiscuous interactions with proteins, and nanoscale assemblies of a glycoconjugate for promoting the proliferation of stem cells or for suppressing immune responses. Subsequently, we emphasize the spatiotemporal control of nanoscale assemblies for controlling the cell fate, particularly illustrate a paradigm-shifting approach—enzyme-instructed self-assembly (EISA), that is, the integration of enzymatic reaction and self-assembly—for generating nanoscale assemblies from innocuous monomers for selectively inhibiting cancer cells. Moreover, we introduce a convenient assay for proteomic study of the proteins that interact with nanoscale assemblies of small molecules in cellular environment. Furthermore, we introduce the use of ligand–receptor interaction to catalyze the formation of nanoscale assemblies. By illustrating these experimental strategies for controlling the formation of nanoscale assemblies of small molecules and for identifying their corresponding protein targets, we aim to highlight that, though not being defined at the genetic level, nanoscale assemblies of small molecules are able to perform many critical biological functions. We envision that nanoscale assemblies of small molecules are a new frontier at the intersection of nanoscience and cell biology and biomedicine. In addition, we discuss the challenges and perspectives of relevant potential biomedical applications of nanoscale assemblies of small molecules.
Co-reporter:Jie Zhou ; Xuewen Du ; Yuan Gao ; Junfeng Shi
Journal of the American Chemical Society 2014 Volume 136(Issue 8) pp:2970-2973
Publication Date(Web):February 10, 2014
DOI:10.1021/ja4127399
Anisotropy or alignment is a critical feature of functional soft materials in living organisms, but it remains a challenge for spontaneously generating anisotropic gel materials. Here we report a molecular design that increases intermolecular aromatic–aromatic interactions of hydrogelators during enzymatic hydrogelation for spontaneously forming an anisotropic hydrogel. This process, relying on both aromatic–aromatic interactions and enzyme catalysis, results in spontaneously aligned supramolecular nanofibers as the matrices of a monodomain hydrogel that exhibits significant birefringence. This work, as the first example of monodomain hydrogels formed via an enzymatic reaction, illustrates a new biomimetic approach for generating aligned anisotropic soft materials.
Co-reporter:Junfeng Shi; Xuewen Du; Yibing Huang; Jie Zhou; Dan Yuan; Dongdong Wu; Ye Zhang; Richard Haburcak; Irving R. Epstein
Journal of the American Chemical Society 2014 Volume 137(Issue 1) pp:26-29
Publication Date(Web):December 18, 2014
DOI:10.1021/ja5100417
Because they exhibit important biological functions, from unfolding proteins to activating enzymes to controlling cell fates, aggregates of small molecules are able to serve as functional molecular entities in cellular environments. However, the inability to precisely control their production has hampered the understanding and exploration of their biological functions. Here we show that the well-established ligand–receptor interaction between vancomycin and d-Ala-d-Ala catalyzes the aggregation of a d-Ala-d-Ala-containing small peptide derivative in water. The resulting aggregates largely adhere to the cell surface to induce cell necroptosis. Mutation of d-Ala-d-Ala to l-Ala-l-Ala or removal of the aromatic group in the derivative results in innocuous compounds, confirming that the aromatic–aromatic and ligand–receptor interactions are responsible for the formation and corresponding cytotoxicity of the aggregates. In addition to being the first example of ligand–receptor interaction-catalyzed aggregation of small molecules on the surface of mammalian cells, this work provides useful insights for understanding the cytotoxicity of molecular aggregates of small molecules.
Co-reporter:Ye Zhang ; Ning Zhou ; Ning Li ; Megan Sun ; Dongshin Kim ; Seth Fraden ; Irving R. Epstein
Journal of the American Chemical Society 2014 Volume 136(Issue 20) pp:7341-7347
Publication Date(Web):April 21, 2014
DOI:10.1021/ja503665t
While living systems have developed highly efficient ways to convert chemical energy (e.g., ATP hydrolysis) to mechanical motion (e.g., movement of muscle), it remains a challenge to build muscle-like biomimetic systems to generate mechanical force directly from chemical reactions. Here we show that a continuous flow of reactant solution leads to by far the largest volume change to date in autonomous active gels driven by the Belousov–Zhabotinsky reaction. These results demonstrate that microfluidics offers a useful and facile experimental approach to optimize the conditions (e.g., fabrication methods, counterions, flow rates, concentrations of reagents) for chemomechanical transduction in active materials. This work thus provides much needed insights and methods for the development of chemomechanically active systems based on combining soft materials and microfluidic systems.
Co-reporter:Yi Kuang, Yuan Gao, Junfeng Shi, Jie Li and Bing Xu
Chemical Communications 2014 vol. 50(Issue 21) pp:2772-2774
Publication Date(Web):22 Jan 2014
DOI:10.1039/C3CC48832B
The conjugation of taurine with a dipeptide derivative affords a cell compatible, small molecular hydrogelator to form hydrogels that exhibit rich phase transition behaviors in response to sonication and the change of pH or temperature.
Co-reporter:Dongdong Wu, Jie Zhou, Junfeng Shi, Xuewen Du and Bing Xu
Chemical Communications 2014 vol. 50(Issue 16) pp:1992-1994
Publication Date(Web):19 Dec 2013
DOI:10.1039/C3CC48946A
Here we report the first example of a hydrogelator made of a conjugate of nucleobase–saccharide–amino acids by incorporating L-3-(2-naphthyl)-alanine to the conjugate, which illustrates a facile and effective method for generating bioactive and functional hydrogelators from the basic biological building blocks.
Co-reporter:Yi Kuang;Xuewen Du;Jie Zhou
Advanced Healthcare Materials 2014 Volume 3( Issue 8) pp:1217-1221
Publication Date(Web):
DOI:10.1002/adhm.201300645
Co-reporter:Xuewen Du, Jie Zhou, Olgun Guvench, Frank O. Sangiorgi, Xinming Li, Ning Zhou, and Bing Xu
Bioconjugate Chemistry 2014 Volume 25(Issue 6) pp:1031
Publication Date(Web):May 5, 2014
DOI:10.1021/bc500187m
The synthetic challenges in glycobiology and glycochemistry hamper the development of glycobiomaterials for biomedicine. Here we report the use of molecular self-assembly to sidestep the laborious synthesis of complex glycans for promoting the proliferation of murine embryonic stem (mES) cells. Our study shows that the supramolecular assemblies of a small molecule conjugate of nucleobase, amino acids, and saccharide, as a de novo glycoconjugate, promote the proliferation of mES cells and the development of zygotes into blastocysts of mouse. Molecular engineering confirms that each motif (i.e., adenine, Arg-Gly-Asp (RGD) domain, and glucosamine) is indispensable for the observed activity of the conjugate. As the first example of using assemblies of the molecular conjugates of multiple fundamental biological building blocks to control cell behaviors, this work illustrates an unprecedented approach to use supramolecular assemblies as multifunctional mimics of glycoconjugates.
Co-reporter:Xuewen Du, Jie Zhou, Liheng Wu, Shouheng Sun, and Bing Xu
Bioconjugate Chemistry 2014 Volume 25(Issue 12) pp:2129
Publication Date(Web):November 28, 2014
DOI:10.1021/bc500516g
As an important and necessary step of sampling biological specimens, the separation of malignant cells from a mixed population of cells usually requires sophisticated instruments and/or expensive reagents. For health care in the developing regions, there is a need for an inexpensive sampling method to capture tumor cells for rapid and accurate diagnosis. Here we show that an underexplored generic difference—overexpression of ectophosphatases—between cancer and normal cells triggers the d-tyrosine phosphate decorated magnetic nanoparticles (Fe3O4-p(d-Tyr)) to adhere selectively on cancer cells upon catalytic dephosphorylation, which enables magnetic separation of cancer cells from mixed population of cells (e.g., cocultured cancer cell (HeLa-GFP) and stromal cells (HS-5)). Moreover, the Fe3O4-p(d-Tyr) nanoparticles also selectively inhibit cancer cells in the coculture. As a general method to broadly target cancer cells without highly specific ligand–receptor interactions (e.g., antibodies), the use of an enzymatic reaction to spatiotemporally modulate the state of various nanostructures in cellular environments will ultimately lead to the development of new theranostic applications of nanomaterials.
Co-reporter:Fan Zhao, Jingyu Li, Ning Zhou, Jiro Sakai, Yuan Gao, Junfeng Shi, Bronia Goldman, Hayley M. Browdy, Hongbo R. Luo, and Bing Xu
Bioconjugate Chemistry 2014 Volume 25(Issue 12) pp:2116
Publication Date(Web):November 14, 2014
DOI:10.1021/bc5004923
Most immunomodulatory materials (e.g., vaccine adjuvants such as alum) modulate adaptive immunity, and yet little effort has focused on developing materials to regulate innate immunity, which get mentioned only when inflammation affects the biocompatibility of biomaterials. Traditionally considered as short-lived effector cells from innate immunity primarily for the clearance of invading microorganisms without specificity, neutrophils exhibit a key role in launching and shaping the immune response. Here we show that the incorporation of unnatural amino acids into a well-known chemoattractant—N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)—offers a facile approach to create a de novo, multifunctional chemoattractant that self-assembles to form supramolecular nanofibrils and hydrogels. This de novo chemoattractant not only exhibits preserved cross-species chemoattractant activity to human and murine neutrophils, but also effectively resists proteolysis. Thus, its hydrogel, in vivo, releases the chemoattractant and attracts neutrophils to the desired location in a sustainable manner. As a novel and general approach to generate a new class of biomaterials for modulating innate immunity, this work offers a prolonged acute inflammation model for developing various new applications.
Co-reporter:Fan Zhao, Balthasar A. Heesters, Isaac Chiu, Yuan Gao, Junfeng Shi, Ning Zhou, Michael C. Carroll and Bing Xu
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 35) pp:6816-6819
Publication Date(Web):23 Jul 2014
DOI:10.1039/C4OB01362J
An L-rhamnose-based hydrogelator self-assembles to form nanofibrils, which, in contrast to the properties of monomeric L-rhamnose, suppress the antibody response of mice to phycoerythrin (PE), a fluorescent protein antigen. As the first example of the supramolecular assemblies of a saccharide to suppress immunity, this work illustrates a new approach of immunomodulation.
Co-reporter:Dan Yuan, Rong Zhou, Junfeng Shi, Xuewen Du, Xinming Li and Bing Xu
RSC Advances 2014 vol. 4(Issue 50) pp:26487-26490
Publication Date(Web):09 Jun 2014
DOI:10.1039/C4RA04765F
We report the first example of the use of enzymes to trigger the self-assembly of the conjugates of nucleobases, amino acids, and saccharide to form supramolecular hydrogels in water, which illustrates a facile approach for the development of a new class of multifunctional soft materials for biomedical applications.
Co-reporter:Dongdong Wu;Xuewen Du;Junfeng Shi;Jie Zhou
Chinese Journal of Chemistry 2014 Volume 32( Issue 4) pp:313-318
Publication Date(Web):
DOI:10.1002/cjoc.201400092
Abstract
Three new hydrogelators based on the conjugates of three naturally occurring biological building blocks: nucleobase, saccharide, and amino acids, were explored. Being synthesized via a facile solid phase peptide synthesis route, the hydrogelators self-assemble in water to afford supramolecular nanofibers and hydrogels. Transmission electron microscopy, oscillation rheometry, and circular dichroism reveal that the hydrogels consist of largely helix-based nanofibers of the widths of 5–12 nm and exhibit storage moduli up to 1 kPa. These hydrogelators also exhibit excellent cell-compatibility. This work illustrates a new platform for constructing molecular soft materials for nanobiotechnology.
Co-reporter:Junfeng Shi, Xuewen Du, Dan Yuan, Jie Zhou, Ning Zhou, Yibing Huang, and Bing Xu
Biomacromolecules 2014 Volume 15(Issue 10) pp:
Publication Date(Web):September 5, 2014
DOI:10.1021/bm5010355
Peptides made of d-amino acids, as the enantiomer of corresponding l-peptides, are able to resist proteolysis. It is, however, unclear or much less explored whether or how d-amino acids affect the cellular response of supramolecular nanofibers formed by enzyme-triggered self-assembly of d-peptides. In this work, we choose a cell compatible molecule, Nap-l-Phe-l-Phe-l-pTyr (LLL-1P), and systematically replace the l-amino acids in this tripeptidic precursor or its hydrogelator by the corresponding d-amino acid(s). The replacement of even one d-amino acid in this tripeptidic precursor increases its proteolytic resistance. The results of static light scattering and TEM images show the formation of nanostructures upon the addition of alkaline phosphatase, even at concentrations below the minimum gelation concentration (mgc). All these isomers are able to form ordered nanostructures and exhibit different morphologies. According to the cell viability assay on these stereochemical isomers, cells exhibit drastically different responses to the enantiomeric precursors, but almost same responses to the enantiomeric hydrogelators. Furthermore, the different cellular responses of LLL-1P and DDD-1P largely originate from the ecto-phosphatases catalyzed self-assembly of DDD-1 on the surface of cells. Therefore, this report not only illustrates a new way for tailoring the properties of supramolecular assemblies, but also provides new insights to answering the fundamental question of how mammalian cells respond to enzymatic formation of nanoscale supramolecular assemblies (e.g., nanofibers) of d-peptides.
Co-reporter:Xuewen Du;Jie Zhou ;Dr. Bing Xu
Chemistry – An Asian Journal 2014 Volume 9( Issue 6) pp:1446-1472
Publication Date(Web):
DOI:10.1002/asia.201301693
Abstract
As a consequence of the self-assembly of small organic molecules in water, supramolecular hydrogels are evolving from serendipitous events during organic synthesis to become a new type of materials that hold promise for applications in biomedicine. In this Focus Review, we describe recent advances in the use of basic biological building blocks for creating molecules that act as hydrogelators and the potential applications of the corresponding hydrogels. After introducing the concept of supramolecular hydrogels and defining the scope of this review, we briefly describe the methods for making and characterizing supramolecular hydrogels. We then discuss representative hydrogelators according to the categories of their building blocks, such as amino acids, nucleobases, and saccharides, and highlight the applications of the hydrogels when necessary. Finally, we offer our perspective and outlook on this fast-growing field at the interface of organic chemistry, materials, biology, and medicine. By providing a snapshot for chemists, engineers, and medical scientists, we hope that this Focus Review will contribute to the development of multidisciplinary research on supramolecular hydrogels for a wide range of applications in different fields.
Co-reporter:Dr. Yi Kuang;Junfeng Shi;Jie Li;Dan Yuan;Kyle A. Alberti; Qiaobing Xu;Dr. Bing Xu
Angewandte Chemie International Edition 2014 Volume 53( Issue 31) pp:8104-8107
Publication Date(Web):
DOI:10.1002/anie.201402216
Abstract
Fibrils formed by proteins are vital components for cells. However, selective formation of xenogenous nanofibrils of small molecules on mammalian cells has yet to be observed. Here we report an unexpected observation of hydrogel/nanonets of a small D-peptide derivative in pericellular space. Surface and secretory phosphatases dephosphorylate a precursor of a hydrogelator to trigger the self-assembly of the hydrogelator and to result in pericellular hydrogel/nanonets selectively around the cancer cells that overexpress phosphatases. Cell-based assays confirm that the pericellular hydrogel/nanonets block cellular mass exchange to induce apoptosis of cancer cells, including multidrug-resistance (MDR) cancer cells, MES-SA/Dx5. Pericellular hydrogel/nanonets of small molecules to exhibit distinct functions illustrates a fundamentally new way to engineer molecular assemblies spatiotemporally in cellular microenvironment for inhibiting cancer cell growth and even metastasis.
Co-reporter:Dr. Yi Kuang;Junfeng Shi;Jie Li;Dan Yuan;Kyle A. Alberti; Qiaobing Xu;Dr. Bing Xu
Angewandte Chemie 2014 Volume 126( Issue 31) pp:8242-8245
Publication Date(Web):
DOI:10.1002/ange.201402216
Abstract
Fibrils formed by proteins are vital components for cells. However, selective formation of xenogenous nanofibrils of small molecules on mammalian cells has yet to be observed. Here we report an unexpected observation of hydrogel/nanonets of a small D-peptide derivative in pericellular space. Surface and secretory phosphatases dephosphorylate a precursor of a hydrogelator to trigger the self-assembly of the hydrogelator and to result in pericellular hydrogel/nanonets selectively around the cancer cells that overexpress phosphatases. Cell-based assays confirm that the pericellular hydrogel/nanonets block cellular mass exchange to induce apoptosis of cancer cells, including multidrug-resistance (MDR) cancer cells, MES-SA/Dx5. Pericellular hydrogel/nanonets of small molecules to exhibit distinct functions illustrates a fundamentally new way to engineer molecular assemblies spatiotemporally in cellular microenvironment for inhibiting cancer cell growth and even metastasis.
Co-reporter:Jiayang Li ; Yuan Gao ; Yi Kuang ; Junfeng Shi ; Xuewen Du ; Jie Zhou ; Huaimin Wang ; Zhimou Yang
Journal of the American Chemical Society 2013 Volume 135(Issue 26) pp:9907-9914
Publication Date(Web):June 6, 2013
DOI:10.1021/ja404215g
d-Peptides, as the enantiomers of the naturally occurring l-peptides, usually resist endogenous proteases and are presumably insensitive to most enzymes. But, it is unclear whether or how a phosphatase catalyzes the dephosphorylation from d-peptides. In this work, we examine the formation of the nanofibers of d-peptides via enzymatic dephosphorylation. By comparing the enzymatic hydrogelation of l-peptide and d-peptide based hydrogelators, we find that the chirality of the precursors of the hydrogelators affects little on the enzymatic hydrogelation resulted from the removal of the phosphate group from a tyrosine phosphate residue. The attachment of a therapeutic agent (e.g., taxol) or a fluorophore (e.g., 4-nitro-2,1,3-benzoxadiazole) to the d-peptide based hydrogelators affords a new type of biostable or biocompatible hydrogelators, which may find applications in intratumoral chemotherapy or intracellular imaging, respectively. This work, as the first comprehensive and systematic study of the unexpected enzymatic dephosphorylation of d-peptides, illustrates a useful approach to generate supramolecular hydrogels that have both biostability and other desired functions.
Co-reporter:Ye Zhang ; Bei Zhang ; Yi Kuang ; Yuan Gao ; Junfeng Shi ; Xi Xiang Zhang
Journal of the American Chemical Society 2013 Volume 135(Issue 13) pp:5008-5011
Publication Date(Web):March 25, 2013
DOI:10.1021/ja402490j
The integration of a tripeptide derivative, which is a versatile self-assembly motif, with a ruthenium(II)tris(bipyridine) complex affords the first supramolecular metallo-hydrogelator that not only self assembles in water to form a hydrogel but also exhibits gel–sol transition upon oxidation of the metal center. Surprisingly, the incorporation of the metal complex in the hydrogelator results in the nanofibers, formed by the self-assembly of the hydrogelator in water, to have the width of a single molecule of the hydrogelator. These results illustrate that metal complexes, besides being able to impart rich optical, electronic, redox, or magnetic properties to supramolecular hydrogels, also offer a unique geometrical control to prearrange the self-assembly motif prior to self-assembling. The use of metal complexes to modulate the dimensionality of intermolecular interactions may also help elucidate the interactions of the molecular nanofibers with other molecules, thus facilitating the development of supramolecular hydrogel materials for a wide range of applications.
Co-reporter:Jiayang Li;Xinming Li;Yi Kuang;Yuan Gao;Xuewen Du;Junfeng Shi
Advanced Healthcare Materials 2013 Volume 2( Issue 12) pp:1586-1590
Publication Date(Web):
DOI:10.1002/adhm.201300041
Abstract
None of the clinical trials of anti-HIV gels based on conventional polymers or lipid emulsions has been successful, suggesting the need of new molecular design of the anti-HIV gels. This paper reports the conversion of anti-HIV prodrugs into self-delivery supramolecular hydrogels. By covalently conjugating reverse transcriptase inhibitors to a versatile self-assembly motif, the hydrogelators that self-assemble to form supramolecular nanofibers as the matrices of hydrogels in a weak acidic condition are obtained. Upon the treatment of prostate acid phosphatase (PAP), the hydrogels exhibit drastically enhanced elasticity. The hydrogelators are biocompatible and able to release the inhibitors under physiological condition. The use of the self-assembly motif as a self-delivery agent containing non-steroid anti-inflammatory drug (NSAID) renders this hydrogel to be both anti-inflammatory and anti-HIV. This work illustrates an unprecedented approach for designing multifunctional supramolecular hydrogels that may serve as potential anti-HIV hydrogels for sustained drug release.
Co-reporter:Yi Kuang, Dan Yuan, Ye Zhang, Anita Kao, Xuewen Du and Bing Xu
RSC Advances 2013 vol. 3(Issue 21) pp:7704-7707
Publication Date(Web):05 Apr 2013
DOI:10.1039/C3RA41523F
Depending on the methods of preparation, amphiphilic small molecules aggregate to form nanostructures with different morphologies that interact with cytosol proteins in a drastically different manner, thus illustrating the first example of morphologically dependent protein binding of nanoscale molecular aggregates.
Co-reporter:Ye Zhang, Rong Zhou, Junfeng Shi, Ning Zhou, Irving R. Epstein, and Bing Xu
The Journal of Physical Chemistry B 2013 Volume 117(Issue 21) pp:6566-6573
Publication Date(Web):May 9, 2013
DOI:10.1021/jp401353e
We study the use of post-self-assembly cross-linking to combine molecular nanofibers of hydrogelators with copolymers to generate oscillatory materials using the Belousov–Zhabotinsky reaction. The formation of nanofibers from designed hydrogelators provides multiple polymerizable sites for copolymerizing with N-isopropylacrylamide and for attaching a catalytic ruthenium bipyridine complex on the copolymer. The combination of supramolecular self-assembly with copolymerization offers a versatile and facile approach for generating soft materials that have large pores in the gel network and robust mechanical integrity. These larger pores facilitate the diffusion of the reactants and accelerate the chemical oscillation by about a factor of 4 relative to a poly(NIPAAm-Ru) gel that contains no molecular nanofibers.
Co-reporter:Yi Kuang ; Bing Xu
Angewandte Chemie 2013 Volume 125( Issue 27) pp:7082-7086
Publication Date(Web):
DOI:10.1002/ange.201302658
Co-reporter:Dr. Ye Zhang;Ning Zhou;Sathish Akella;Yi Kuang;Dr. Dongshin Kim;Alyssa Schwartz;Marc Bezpalko;Dr. Bruce M. Foxman;Dr. Seth Fraden;Dr. Irving R. Epstein;Dr. Bing Xu
Angewandte Chemie International Edition 2013 Volume 52( Issue 44) pp:11494-11498
Publication Date(Web):
DOI:10.1002/anie.201304437
Co-reporter:Yi Kuang ; Bing Xu
Angewandte Chemie International Edition 2013 Volume 52( Issue 27) pp:6944-6948
Publication Date(Web):
DOI:10.1002/anie.201302658
Co-reporter:Yuan Gao, Yi Kuang, Xuewen Du, Jie Zhou, Preethi Chandran, Ferenc Horkay, and Bing Xu
Langmuir 2013 Volume 29(Issue 49) pp:15191-15200
Publication Date(Web):November 22, 2013
DOI:10.1021/la403457c
Self-assembly of small molecules, as a more common phenomenon than one previously thought, can be either beneficial or detrimental to cells. Despite its profound biological implications, how the self-assembly of small molecules behave in a cellular environment is largely unknown and barely explored. This work studies four fluorescent molecules that consist of the same peptidic backbone (e.g., Phe–Phe–Lys) and enzyme trigger (e.g., a phosphotyrosine residue), but bear different fluorophores on the side chain of the lysine residue of the peptidic motif. These molecules, however, exhibit a different ability of self-assembly before and after enzymatic transformation (e.g., dephosphorylation). Fluorescent imaging reveals that self-assembly directly affects the distribution of these small molecules in a cellular environment. Moreover, cell viability tests suggest that the states and the locations of the molecular assemblies in the cellular environment control the phenotypes of the cells. For example, the molecular nanofibers of one of the small molecules apparently stabilize actin filaments and alleviate the insult of an F-actin toxin (e.g., latrunculin A). Combining fluorescent imaging and enzyme-instructed self-assembly of small peptidic molecules, this work demonstrates self-assembly as a key factor for dictating the spatial distribution of small molecules in a cellular environment. In addition, it illustrates a useful approach, based on enzyme-instructed self-assembly of small molecules, to modulate spatiotemporal profiles of small molecules in a cellular environment, which allows the use of the emergent properties of small molecules to control the fate of cells.
Co-reporter:Yuan Gao, Cristina Berciu, Yi Kuang, Junfeng Shi, Daniela Nicastro, and Bing Xu
ACS Nano 2013 Volume 7(Issue 10) pp:9055
Publication Date(Web):September 25, 2013
DOI:10.1021/nn403664n
Like cellular proteins that form fibrillar nanostructures, small hydrogelator molecules self-assemble in water to generate molecular nanofibers. In contrast to the well-defined (dys)functions of endogenous protein filaments, the fate of intracellular assembly of small molecules remains largely unknown. Here we demonstrate the imaging of enzyme-triggered self-assembly of nonfluorescent small molecules by doping the molecular assemblies with a fluorescent hydrogelator. The cell fractionation experiments, fluorescent imaging, and electron microscopy indicate that the hydrogelators self-assemble and localize to the endoplasmic reticulum (ER) and are likely processed via the cellular secretory pathway (i.e., ER–Golgi–lysosomes/secretion). This work, as the first example of the use of correlative light and electron microscopy for probing the self-assembly of nonfluorescent small molecules inside live mammalian cells, not only establishes a general strategy to provide the spatiotemporal profile of the assemblies of small molecules inside cells but may lead to a new paradigm for regulating cellular functions based on the interactions between the assemblies of small molecules (e.g., molecular nanofibers) and subcellular organelles.Keywords: enzyme; intracellular; localization; nanofibers; self-assembly; small molecule
Co-reporter:Yue Pan, Xuewen Du, Fan Zhao and Bing Xu
Chemical Society Reviews 2012 vol. 41(Issue 7) pp:2912-2942
Publication Date(Web):08 Feb 2012
DOI:10.1039/C2CS15315G
In the rapidly developing areas of nanobiotechnology, magnetic nanoparticles (MNPs) are one type of the most well-established nanomaterials because of their biocompatibility and the potential applications as alternative contrast enhancing agents for magnetic resonance imaging (MRI). While the development of MNPs as alternative contrast agents for MRI application has moved quickly to testing in animal models and clinical trials, other applications of biofunctional MNPs have been explored extensively at the stage of qualitative or conceptual demonstration. In this critical review, we summarize the development of two straightforward applications of biofunctional MNPs—manipulating proteins and manipulating cells—in the last five years or so and hope to provide a relatively comprehensive assessment that may help the future developments. Specifically, we start with the examination of the strategy for the surface functionalization of MNPs because the applications of MNPs essentially depend on the molecular interactions between the functional molecules on the MNPs and the intended biological targets. Then, we discuss the use of MNPs for manipulating proteins since protein interactions are critical for biological functions. Afterwards, we evaluate the development of the use of MNPs to manipulate cells because the response of MNPs to a magnetic field offers a unique way to modulate cellular behavior in a non-contact or “remote” mode (i.e. the magnet exerts force on the cells without direct contact). Finally, we provide a perspective on the future directions and challenges in the development of MNPs for these two applications. By reviewing the examples of the design and applications of biofunctional MNPs, we hope that this article will provide a reference point for the future development of MNPs that address the present challenges and lead to new opportunities in nanomedicine and nanobiotechnology (137 references).
Co-reporter:Jiayang Li ; Yi Kuang ; Yuan Gao ; Xuewen Du ; Junfeng Shi
Journal of the American Chemical Society 2012 Volume 135(Issue 2) pp:542-545
Publication Date(Web):November 8, 2012
DOI:10.1021/ja310019x
As systemically used therapeutics for treating acute or chronic pains or inflammations, nonsteroidal anti-inflammatory drugs (NSAIDs) also associate with the adverse gastrointestinal and renal effects and cardiovascular risks. Thus, it is beneficial to develop topical gels that selectively inhibit cyclooxygenase-2 (COX-2) for the management of local inflammation. In this work, we demonstrate that the covalent conjugation of d-amino acids to naproxen (i.e., a NSAID) not only affords supramolecular hydrogelators for the topical gels but also unexpectedly and significantly elevates the selectivity toward COX-2 about 20× at little expense of the activity of naproxen. This work illustrates a previously unexplored approach that employs d-amino acids for the development of functional molecules that have dual or multiple roles and exceptional biostability, which offers a new class of molecular hydrogels of therapeutic agents.
Co-reporter:Yue Pan, Marcus J. C. Long, Hsin-Chieh Lin, Lizbeth Hedstrom and Bing Xu
Chemical Science 2012 vol. 3(Issue 12) pp:3495-3499
Publication Date(Web):10 Sep 2012
DOI:10.1039/C2SC20519J
This work reports the first example of the biofunctional magnetic nanoparticles as a “magnetic dock” for directly sorting proteins inside live cells. We decorate the iron oxide nanoparticles with the ligands that bind selectively to fusion proteins consisting of the proteins of interest (POIs) and the ligand receptors. Similar to protein sorting processes on vesicles, the clusters of these functionalized magnetic nanoparticles only bind to the fusion proteins via the interaction with the receptors, but exhibit little interaction to other proteins. This work demonstrates new applications of magnetic nanoparticles and may ultimately contribute to the exploration of the functions of proteins via the selective, spatiotemporal control of the proteins by a magnetic force.
Co-reporter:Yuan Gao, Marcus J. C. Long, Junfeng Shi, Lizbeth Hedstrom and Bing Xu
Chemical Communications 2012 vol. 48(Issue 67) pp:8404-8406
Publication Date(Web):03 Jul 2012
DOI:10.1039/C2CC33631F
Here we report the first example of the use of supramolecular hydrogels to discover the protein targets of aggregates of small molecules.
Co-reporter:Zhimou Yang, Yi Kuang, Xinming Li, Ning Zhou, Ye Zhang and Bing Xu
Chemical Communications 2012 vol. 48(Issue 74) pp:9257-9259
Publication Date(Web):26 Jul 2012
DOI:10.1039/C2CC34935C
As the first example of hydrogelator derived from aminoglycoside antibiotics, the hydrogel of kanamycin indicates that the hydrogel of aminoglycosides preserve the specific interaction with their macromolecular targets (e.g., 16S rRNA), thus illustrating a simple approach to explore and identify possible biological targets of supramolecular nanofibers/hydrogels.
Co-reporter:Xinming Li, Xuewen Du, Yuan Gao, Junfeng Shi, Yi Kuang and Bing Xu
Soft Matter 2012 vol. 8(Issue 28) pp:7402-7407
Publication Date(Web):14 Jun 2012
DOI:10.1039/C2SM25725D
Here we report the generation of a novel class of supramolecular hydrogelators based on the integration of nucleobases, Arg-Gly-Asp (RGD) peptides, and glucosamine in a single molecule. These novel small molecule hydrogelators self-assemble in water to form stable supramolecular nanofibers/hydrogels and exhibit useful biostability. This approach provides a new opportunity for systematic exploration of the self-assembly of small biomolecules by varying any individual segment to generate a large array of supramolecular hydrogels for biological functions and for biomedical applications.
Co-reporter:Xinming Li, Yi Kuang and Bing Xu
Soft Matter 2012 vol. 8(Issue 10) pp:2801-2806
Publication Date(Web):10 Jan 2012
DOI:10.1039/C2SM06920B
This highlight introduces the development of hydrogelators consisting of nucleobases, amino acids, and glycosides (i.e., molecular trinity), or nucleobases and amino acids (i.e., nucleopeptides). These novel small molecule hydrogelators self-assemble in water to form stable supramolecular nanofibers/hydrogels and exhibit useful biological properties (e.g., biocompatibility, biostability, and the ability to bind and transport DNA into live cells). The approach discussed here not only provides a new strategy to develop soft biomaterials as a form of nanomedicines, but also contributes to the understanding of molecular self-assembly in water by modulating the non-covalent interactions derived from the three basic building blocks used in living organisms.
Co-reporter:Ye Zhang, Ning Li, Jorge Delgado, Ning Zhou, Ryo Yoshida, Seth Fraden, Irving R. Epstein and Bing Xu
Soft Matter 2012 vol. 8(Issue 26) pp:7056-7061
Publication Date(Web):31 May 2012
DOI:10.1039/C2SM25797A
We designed and synthesised two new polymerizable ruthenium complexes that catalyse the Belousov–Zhabotinsky (BZ) oscillating reaction and incorporated them into a copolymer to form hydrogels. The periodic oxidation and reduction of the attached ruthenium complex in the BZ reaction induces hydrating and dehydrating effects, respectively, that result in self-oscillatory volume changes of the hydrogel. We evaluated the correlation between the chemomechanical oscillation properties of the hydrogel and the proximity of the catalyst to the polymer backbone. Our results indicate that, like the change of such macroscopic parameters as temperature, reactant concentrations and pH, varying the microscopic distance between the catalyst and the polymeric chain provides a new way to tailor the chemomechanical behaviour, e.g., the initiation time, the frequency of oscillation, and the volume change of BZ hydrogels. Moreover, variation of the catalysts offers a new means to control the microstructure of the copolymer by expanding the range of monomer ratios. Modulation of molecular structure appears to be an effective way to alter the reaction–diffusion profile of species within heterogeneous chemoresponsive gels, thus contributing to the development of multifunctional, active soft materials capable of converting chemical energy into controllable mechanical forces.
Co-reporter:Ye Zhang, Ning Li, Jorge Delgado, Yuan Gao, Yi Kuang, Seth Fraden, Irving R. Epstein, and Bing Xu
Langmuir 2012 Volume 28(Issue 6) pp:3063-3066
Publication Date(Web):January 25, 2012
DOI:10.1021/la203923d
After a polymerizable hydrogelator self-assembles in water to form molecular nanofibers, post-self-assembly cross-linking allows the catalyst of the Belousov–Zhabotinsky (BZ) reaction to be attached to the nanofibers, resulting in a hydrogel that exhibits concentration oscillations, spiral waves, and concentric waves. In addition to the first report of the observation of BZ spiral waves in a hydrogel that covalently integrates the catalyst, we suggest a new approach to developing active soft materials as chemical oscillators and for exploring the correlation between molecular structure and far-from-equilibrium dynamics.
Co-reporter:Xinming Li, Xuewen Du, Jiayang Li, Yuan Gao, Yue Pan, Junfeng Shi, Ning Zhou, and Bing Xu
Langmuir 2012 Volume 28(Issue 37) pp:13512-13517
Publication Date(Web):August 20, 2012
DOI:10.1021/la302583a
Here we report the examination of two convenient strategies, the use of a d-amino acid residue or a glycoside segment, for increasing the proteolytic resistance of supramolecular hydrogelators based on small peptides. Our results show that the introduction of d-amino acid or glycoside to the peptides significantly increases the resistance of the hydrogelators against proteinase K, a powerful endopeptidase. The insertion of d-amino acid in the peptide backbone, however, results relatively low storage moduli of the hydrogels, likely due to the disruption of the superstructures of the molecular assembly. In contrast, the introduction of a glycoside to the C-terminal of peptide enhances the biostability of the hydrogelators without the significant decrease of the storage moduli of the hydrogels. This work suggests that the inclusion of a simple glycogen in hydrogelators is a useful approach to increase their biostability, and the gained understanding from the work may ultimately lead to development of hydrogels of functional peptides for biomedical applications that require long-term biostability.
Co-reporter:Xinming Li ; ; Junfeng Shi ; Yuan Gao ; Hsin-Chieh Lin
Journal of the American Chemical Society 2011 Volume 133(Issue 43) pp:17513-17518
Publication Date(Web):September 19, 2011
DOI:10.1021/ja208456k
The integration of nucleobase, amino acid, and glycoside into a single molecule results in a novel class of supramolecular hydrogelators, which not only exhibit biocompatibility and biostability but also facilitate the entry of nucleic acids into cytosol and nuclei of cells. This work illustrates a simple way to generate an unprecedented molecular architecture from the basic biological building blocks for the development of sophisticated soft nanomaterials, including supramolecular hydrogels.
Co-reporter:Marcus J. C. Long ; Yue Pan ; Hsin-Chieh Lin ; Lizbeth Hedstrom
Journal of the American Chemical Society 2011 Volume 133(Issue 26) pp:10006-10009
Publication Date(Web):June 10, 2011
DOI:10.1021/ja202767g
On the basis of the high affinity binding of trimethoprim (TMP) to Escherichia coli dihydrofolate reductase (eDHFR), TMP-decorated iron oxide nanoparticles bind to eDHFR with high affinity and specificity, which allows magnetic modulation of focal adhesion of mammalian cells adhered to a surface. Besides being the first example of nanoparticles that selectively bind to eDHFR, the biocompatibility of the conjugate of TMP–iron oxide nanoparticles renders a convenient and versatile platform for investigating the cellular responses to specific, mechanical perturbation of proteins via a magnetic force.
Co-reporter:Yue Pan, Marcus J. C. Long, Xinming Li, Junfeng Shi, Lizbeth Hedstrom and Bing Xu
Chemical Science 2011 vol. 2(Issue 5) pp:945-948
Publication Date(Web):03 Mar 2011
DOI:10.1039/C1SC00030F
Iron oxide-based magnetic nanoparticles (MNP) surface-decorated with glutathione (GSH) via a dopamine anchor bind to human α1-glutathione S-transferase (GST) with high affinity and specificity and are able to separate GST fusion proteins from cell lysates. Both the purified GST and the protein of interest (POI) preserve their innate properties. The conjugate of MNP and the GST fusion protein also enables magnetic manipulation of cells.
Co-reporter:Yue Pan, Yuan Gao, Junfeng Shi, Ling Wang and Bing Xu
Journal of Materials Chemistry A 2011 vol. 21(Issue 19) pp:6804-6806
Publication Date(Web):04 Apr 2011
DOI:10.1039/C1JM10822K
Here we report a novel supramolecular hydrogelator, which contains a nitrilotriacetic acid (NTA) motif, to form a magnetorheological hydrogel upon interacting with nickel particles or holmium ions or to afford a hydrogel as an efficient absorber of metal ions.
Co-reporter:Fan Zhao, Christopher S. Weitzel, Yuan Gao, Hayley M. Browdy, Junfeng Shi, Hsin-Chieh Lin, Susan T. Lovett and Bing Xu
Nanoscale 2011 vol. 3(Issue 7) pp:2859-2861
Publication Date(Web):02 Jun 2011
DOI:10.1039/C1NR10333D
Here we report the first example of using β-galactosidase to trigger the formation of cell compatible, supramolecular nanofibers, which ultimately may lead to a new approach for the development of soft nanotechnology.
Co-reporter:Yi Kuang, Yuan Gao and Bing Xu
Chemical Communications 2011 vol. 47(Issue 47) pp:12625-12627
Publication Date(Web):31 Oct 2011
DOI:10.1039/C1CC15577F
Consisting of N-terminated diphenylalanine, a new type of supramolecular hydrogelators forms hydrogels within a narrow pH window (pH 5.0 to 6.0) and selectively inhibits growth of HeLa cells, which provides important and useful insights for designing molecular nanofibers as potential nanomedicines.
Co-reporter:Bengang Xing, Tingting Jiang, Wuguo Bi, Yanmei Yang, Lihua Li, Manlun Ma, Chi-Kwong Chang, Bing Xu and Edwin Kok Lee Yeow
Chemical Communications 2011 vol. 47(Issue 5) pp:1601-1603
Publication Date(Web):26 Nov 2010
DOI:10.1039/C0CC04434B
A simple and specific divalent vancomycin–porphyrin has been developed. This divalent vancomycin–porphyrin conjugate indicates promising properties in fluorescent imaging and photodynamic inactivation of vancomycin-sensitive and vancomycin-resistant enterococci (VRE) bacterial strains.
Co-reporter:Yi Kuang, Yuan Gao, Junfeng Shi, Hsin-Chieh Lin and Bing Xu
Chemical Communications 2011 vol. 47(Issue 31) pp:8772-8774
Publication Date(Web):24 Jun 2011
DOI:10.1039/C1CC13115J
Imparting aromatic–aromatic interactions to the potassium binding epitope affords a supramolecular hydrogelator that responds to the K+ concentration by self-assembly into nanofibers of different widths and crosslinking patterns, which illustrates a simple approach to generate biomimic materials based on tunable, hierarchical self-assembly of small molecules.
Co-reporter:Dr. Xinming Li;Yi Kuang;Dr. Hsin-Chieh Lin;Yuan Gao;Junfeng Shi ; Bing Xu
Angewandte Chemie International Edition 2011 Volume 50( Issue 40) pp:9365-9369
Publication Date(Web):
DOI:10.1002/anie.201103641
Co-reporter:Fan Zhao, Yuan Gao, Junfeng Shi, Hayley M. Browdy, and Bing Xu
Langmuir 2011 Volume 27(Issue 4) pp:1510-1512
Publication Date(Web):December 8, 2010
DOI:10.1021/la103982e
The hydrolysis of the carboxylic ester bond, by a base or catalyzed by an enzyme under weak basic conditions, serves as the only path to obtain a novel anisotropic supramolecular hydrogel that is stable over a wide pH range. This result not only expands the molecular scope of supramolecular hydrogelators but also illustrates the design principles for creating pH-stable supramolecular soft materials.
Co-reporter:Junfeng Shi, Yuan Gao, Ye Zhang, Yue Pan, and Bing Xu
Langmuir 2011 Volume 27(Issue 23) pp:14425-14431
Publication Date(Web):October 6, 2011
DOI:10.1021/la2033862
Learning from the stabilization of protein structures, we combine aromatic–aromatic and electrostatic interactions to tailor the elasticity of supramolecular hydrogels. Specifically, calcium ions allow interfiber cross-links among the supramolecular nanofibers of small peptides that consist of multiple carboxylic acid and aromatic groups. A small change in the concentration of calcium increases the elasticity of hydrogels over several orders of magnitude. This simple approach not only demonstrates a biomimetic design of materials but also confirms that the combination of multiple aromatic–aromatic interactions and multiple calcium salt bridges is a feasible way to control the mechanical properties of soft nanomaterials.
Co-reporter:Dr. Xinming Li;Yi Kuang;Dr. Hsin-Chieh Lin;Yuan Gao;Junfeng Shi ; Bing Xu
Angewandte Chemie 2011 Volume 123( Issue 40) pp:9537-9541
Publication Date(Web):
DOI:10.1002/ange.201103641
Co-reporter:Ye Zhang, Yi Kuang, Yuan Gao, and Bing Xu
Langmuir 2011 Volume 27(Issue 2) pp:529-537
Publication Date(Web):July 7, 2010
DOI:10.1021/la1020324
This feature article introduces new structural motifs (referred as “samogen”) that serve as the building blocks of hydrogelators for molecular self-assembly in water to result in a series of supramolecular hydrogels. Using a compound that consists of two phenylalanine residues and a naphthyl group (also abbreviated as NapFF (1) in this text) as an example of the samogens, we demonstrated the ability of the samogens to convert bioactive molecules into molecular hydrogelators that self-assemble in water to result in nanofibers. By briefly summarizing the properties and applications (e.g., wound healing, drug delivery, controlling cell fate, typing bacteria, and catalysis) of these molecular hydrogelators derived from the samogens, we intend to illustrate the basic requirements and promises of the small-molecule hydrogelators for applications in chemistry, materials science, and biomedicine.
Co-reporter:Yuan Gao, Fan Zhao, Qigang Wang, Ye Zhang and Bing Xu
Chemical Society Reviews 2010 vol. 39(Issue 9) pp:3425-3433
Publication Date(Web):12 Jul 2010
DOI:10.1039/B919450A
Enzymes, together with the process of self-assembly, constitute necessary components of the foundation of life on the nanometre scale. The exceedingly high efficiency and selectivity exhibited by enzymes for catalyzing biotransformations naturally lead to the exploration of enzyme mimics and the applications of enzymes in industrial biotransformations. While the mimicking of enzymes aims to preserve the essence of enzymes in a simpler system than proteins, industrial biotransformations demand high activity and stability of enzymes. Recent research suggests that small peptide-based nanofibers in the form of molecular hydrogels can provide a general platform to achieve both important goals. This tutorial review will introduce the recent progress of these research activities on small peptide-based nanomaterials for catalysis and hopes to provide a starting point for further explorations that ultimately may lead to practical applications of enzymes and enzyme mimics for addressing important societal problems in energy, environment, and health.
Co-reporter:Xinming Li ; Jiayang Li ; Yuan Gao ; Yi Kuang ; Junfeng Shi
Journal of the American Chemical Society 2010 Volume 132(Issue 50) pp:17707-17709
Publication Date(Web):December 1, 2010
DOI:10.1021/ja109269v
Conjugation of tripeptide derivatives with olsalazine, a clinically used anti-inflammatory prodrug, yields small molecules that self-assemble in water to form supramolecular hydrogels that undergo a gel-to-sol phase transition upon reduction, resulting in the controlled release of 5-aminosalicylic acid as the anti-inflammatory agent. This methodology will ultimately lead to new biomaterials for site-specific drug delivery.
Co-reporter:Manlung Ma ; Yi Kuang ; Yuan Gao ; Yan Zhang ; Ping Gao
Journal of the American Chemical Society 2010 Volume 132(Issue 8) pp:2719-2728
Publication Date(Web):February 4, 2010
DOI:10.1021/ja9088764
In this paper we report the conjugation of an aromatic moiety (pyrene (P), fluorene (F), or naphthalene (N)) to pentapeptides GAGAS (1), GVPVP (2), VPGVG (3), VTEEI (4), VYGGG (5), and YGFGG (6) to afford peptidic derivatives for exploring pentapeptide-based hydrogels as potential biomaterials. Most of these compounds (1F, 1P, 2F, 2P, 4F, 4P, 4N, 5F, 5N, 6F, 6P, and 6N) behave as molecular hydrogelators and can form hydrogels at minimum concentrations of gelation from 0.5 to 2.8 wt %. The fluorescence spectra of the hydrogels exhibit a significant red shift, indicating the interactions between the aromatic moieties in those hydrogels. The circular dichroism spectra indicate that the self-assembly of the hydrogelators affords helical or β-sheet-like structures. Transmission and scanning electron microscopic examination reveals the nanofiber networks of these hydrogelators. In addition, rheological measurements show fair to excellent viscoelastic properties of these hydrogels. The balance of intermolecular aromatic−aromatic interactions and hydrogen bonds of these hydrogelators leads to their self-assembly in water and the formation of nanofibers as the matrixes of hydrogels. A total of 6 of these 18 pentapeptide derivatives—1N, 2N, 3F, 3P, 3N, and 5P—fail to form hydrogels under the conditions tested, likely due to unbalanced intermolecular interactions. This work suggests that aromatic−aromatic interactions are useful and favorable forces for creating molecular nanofibers and supramolecular hydrogels.
Co-reporter:Zhimou Yang, Ling Wang, Jingyu Wang, Ping Gao and Bing Xu
Journal of Materials Chemistry A 2010 vol. 20(Issue 11) pp:2128-2132
Publication Date(Web):25 Jan 2010
DOI:10.1039/B922858F
In this study, we report multi-component supramolecular hydrogels that exhibit exceptional high storage moduli and a rapid recovery of their original mechanical strength after removing external forces. The formation of such kind of supramolecular hydrogels is simple and versatile, and the components can be easily synthesized or commercially available in large quantities. The supramolecular hydrogels have been characterized by SEM and fluorescence spectrometry and the results obtained by both techniques correlate well with their mechanical properties. They have potential to be developed into useful materials that require high mechanical stiffness and possess rapid recovery properties, such as the injectable immobilization matrix for cells culture, drug release, enzyme encapsulation, etc.
Co-reporter:Xinming Li, Yuan Gao, Yi Kuang and Bing Xu
Chemical Communications 2010 vol. 46(Issue 29) pp:5364-5366
Publication Date(Web):28 Jun 2010
DOI:10.1039/C0CC00163E
This paper reports the first example of the use of an enzymatic reaction to generate a photoresponsive hydrogelator, which represents a convenient route to expand the scope of optically controlled molecular self-assembly in water.
Co-reporter:Yue Pan, Jinhao Gao, Bei Zhang, Xixiang Zhang and Bing Xu
Langmuir 2010 Volume 26(Issue 6) pp:4184-4187
Publication Date(Web):December 11, 2009
DOI:10.1021/la904067q
Nanoparticles that self-assemble on a liquid−liquid interface serve as the building block for making heterodimeric nanostructures. Specifically, hollow iron oxide nanoparticles within hexane form colloidosomes in the aqueous solution of silver nitrate, and iron oxide exposed to the aqueous phase catalyzes the reduction of silver ions to afford a heterodimer of silver and hollow iron oxide nanoparticles. Transmission electron microscopy, selected area electron diffraction, energy-dispersive X-ray spectrometry, X-ray diffraction, UV−vis spectroscopy, and SQUID were used to characterize the heterodimers. Interestingly, the formation of silver nanoparticles helps the removal of spinglass layer on the hollow iron oxide nanoparticles. This work demonstrates a powerful yet convenient strategy for producing sophisticated, multifunctional nanostructures.
Co-reporter:Fan Zhao, Man Lung Ma and Bing Xu
Chemical Society Reviews 2009 vol. 38(Issue 4) pp:883-891
Publication Date(Web):12 Feb 2009
DOI:10.1039/B806410P
This tutorial review aims to introduce a new kind of biomaterials—molecular hydrogels of therapeutic agents. Based on the molecular self-assembly in water, it is possible to transform therapeutic agents into analogues that form hydrogels without compromising their pharmacological efficacy. This transformation can be beneficial in three aspects: (i) the therapeutic agents become “self-deliverable” in the form of hydrogels; (ii) the self-assembly of hydrogelators of drugs might confer new and useful properties such as multivalency or high local densities; (iii) the exploration of molecular hydrogels of drugs may ultimately lead to bioactive molecules that have dual or multiple roles. By summarizing the reports on the molecular hydrogels made from clinical used drugs or other bioactive molecules, this article presents representative molecular hydrogels of therapeutics and outlines the promises and challenges for developing this new class of biomaterials.
Co-reporter:Jinhao Gao, Hongwei Gu and Bing Xu
Accounts of Chemical Research 2009 Volume 42(Issue 8) pp:1097
Publication Date(Web):May 28, 2009
DOI:10.1021/ar9000026
The combination of nanotechnology and molecular biology has developed into an emerging research area: nanobiotechnology. Magnetic nanoparticles are well-established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI). As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging. Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional magnetic nanoparticles. Currently, there are two strategies to fabricate magnetic nanoparticle-based multifunctional nanostructures. The first, molecular functionalization, involves attaching antibodies, proteins, and dyes to the magnetic nanoparticles. The other method integrates the magnetic nanoparticles with other functional nanocomponents, such as quantum dots (QDs) or metallic nanoparticles. Because they can exhibit several features synergistically and deliver more than one function simultaneously, such multifunctional magnetic nanoparticles could have unique advantages in biomedical applications. In this Account, we review examples of the design and biomedical application of multifunctional magnetic nanoparticles. After their conjugation with proper ligands, antibodies, or proteins, the biofunctional magnetic nanoparticles exhibit highly selective binding. These results indicate that such nanoparticles could be applied to biological medical problems such as protein purification, bacterial detection, and toxin decorporation. The hybrid nanostructures, which combine magnetic nanoparticles with other nanocomponents, exhibit paramagnetism alongside features such as fluorescence or enhanced optical contrast. Such structures could provide a platform for enhanced medical imaging and controlled drug delivery. We expect that the combination of unique structural characteristics and integrated functions of multicomponent magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nanomedicine.
Co-reporter:Zhimou Yang, Manlung Ma and Bing Xu
Soft Matter 2009 vol. 5(Issue 13) pp:2546-2548
Publication Date(Web):05 Jun 2009
DOI:10.1039/B908206A
Here we report the first example of using MMP-9 to catalyze the formation and self-assembly of a supramolecular hydrogelator and subsequent hydrogelation.
Co-reporter:Jinhao Gao, Bing Xu
Nano Today 2009 Volume 4(Issue 1) pp:37-51
Publication Date(Web):February 2009
DOI:10.1016/j.nantod.2008.10.009
The successful and explosive development of nanomaterials inevitably leads to their intersections with biology and medicine, which results in increased efforts on nanobiotechnology (or bionanotechnology) research. To focus on one of the most important and fascinating subjects in nanobiotechnology, this review describes the applications of various types of nanomaterials inside cells ranging from cell imaging and cell tracking to cancer treatment. We bring forth the examples with different types of nanomaterials acting inside cells and discuss the challenges and perspectives for their relevant biomedical applications.
Co-reporter:Gaolin Liang, Zhimou Yang, Rongjun Zhang, Lihua Li, Yijun Fan, Yi Kuang, Yuan Gao, Ting Wang, W. William Lu and Bing Xu
Langmuir 2009 Volume 25(Issue 15) pp:8419-8422
Publication Date(Web):March 16, 2009
DOI:10.1021/la804271d
A supramolecular hydrogel based on d-amino acids, which resists hydrolysis catalyzed by proteinase K and offers long-term biostability, exhibits controlled release in vivo, as proved by the pharmacokinetics of encapsulated 125I tracers and the SPECT imaging of the hydrogel-encapsulated 131I tracers. As the first in vivo imaging investigation of the drug release properties of the supramolecular hydrogel, isotope encapsulation serves as a valid, useful assay for characterizing the controlled release properties of supramolecular hydrogels in vivo. Our results indicate that supramolecular hydrogels promise new biomaterials for controlled drug release.
Co-reporter:Qigang Wang Dr.;Lihua Li
Chemistry - A European Journal 2009 Volume 15( Issue 13) pp:3168-3172
Publication Date(Web):
DOI:10.1002/chem.200801653
Co-reporter:Jinhao Gao, Bing Xu
Nano Today 2009 Volume 4(Issue 3) pp:281
Publication Date(Web):June 2009
DOI:10.1016/j.nantod.2009.05.002
Co-reporter:Bing Xu
Langmuir 2009 Volume 25(Issue 15) pp:8375-8377
Publication Date(Web):May 19, 2009
DOI:10.1021/la900987r
This perspective focuses on the potential uses of gels as materials in biological and medical applications. It describes how molecular self-assembly can confer well-defined secondary structures (e.g., nanofibers, nanotubes, and nanospheres) in a liquid that initiates functions within biological systems. Some prospects for future development and the challenges for achieving them are discussed.
Co-reporter:Huaimin Wang, Zhaoqianqi Feng, Bing Xu
Advanced Drug Delivery Reviews (February 2017) Volumes 110–111() pp:102-111
Publication Date(Web):1 February 2017
DOI:10.1016/j.addr.2016.04.008
Nanostructures formed by peptides that self-assemble in water through non-covalent interactions have attracted considerable attention because peptides possess several unique advantages, such as modular design and easiness of synthesis, convenient modification with known functional motifs, good biocompatibility, low immunogenicity and toxicity, inherent biodegradability, and fast responses to a wide range of external stimuli. After about two decades of development, peptide-based supramolecular nanostructures have already shown great potentials in the fields of biomedicine. Among a range of biomedical applications, using such nanostructures for cancer therapy has attracted increased interests since cancer remains the major threat for human health. Comparing with L-peptides, nanostructures containing peptides made of D-amino acid (i.e., D-peptides) bear a unique advantage, biostability (i.e., resistance towards most of endogenous enzymes). The exploration of nanostructures containing D-amino acids, especially their biomedical applications, is still in its infancy. Herein we review the recent progress of D-amino acid-containing supramolecular nanofibers as an emerging class of biomaterials that exhibit unique features for the development of cancer therapeutics. In addition, we give a brief perspective about the challenges and promises in this research direction.Download high-res image (200KB)Download full-size image
Co-reporter:Yuan Gao ; Yi Kuang ; Zu-Feng Guo ; Zhihong Guo ; Isaac J. Krauss
Journal of the American Chemical Society () pp:
Publication Date(Web):September 4, 2009
DOI:10.1021/ja904411z
By covalently connecting taxol with a motif that is prone to self-assemble, we successfully generate the precursor (5a), the hydrogelator (5b), and hydrogel of a taxol derivative without compromising the cytotoxic activity of the taxol. This approach promises a general method to create nanofibers of therapeutic molecules that have a dual role, as both the delivery vehicle and the drug itself.
Co-reporter:Dan Yuan and Bing Xu
Journal of Materials Chemistry A 2016 - vol. 4(Issue 34) pp:NaN5649-5649
Publication Date(Web):2016/07/26
DOI:10.1039/C6TB01592A
Supramolecular hydrogels, formed via intermolecular interactions in water, are emerging as a new type of versatile soft materials to be applied in many areas, such as biomedical applications, catalysis, food additives, and cosmetics. While most of the supramolecular hydrogels are homotypic (i.e., one type of building block), heterotypic supramolecular hydrogels are less explored, but may offer unique advantages. This review describes supramolecular hydrogels that consist of more than one type of building block (i.e., heterotypic) to illustrate the promise and challenges of heterotypic supramolecular hydrogels as soft biomaterials. First, we discuss the driving forces for producing heterotypic supramolecular hydrogels. Second, we introduce the general methods for triggering heterotypic supramolecular hydrogels. Third, we summarize examples of heterotypic supramolecular hydrogels made of hydrogelators with or without amino acid residues. Fourth, we describe the applications of heterotypic supramolecular hydrogels to date. Finally, we give an outlook and propose a few future directions that likely are worthy to explore.
Co-reporter:Xuewen Du, Junfeng Li, Yuan Gao, Yi Kuang and Bing Xu
Chemical Communications 2012 - vol. 48(Issue 15) pp:NaN2100-2100
Publication Date(Web):2011/12/16
DOI:10.1039/C2CC16723A
The use of enzyme to instruct the self-assembly of the nucleoside of adenosine in water provides a new class of molecular nanofibers/hydrogels as functional soft materials.
Co-reporter:Huaimin Wang, Zhaoqianqi Feng and Bing Xu
Chemical Society Reviews 2017 - vol. 46(Issue 9) pp:NaN2436-2436
Publication Date(Web):2017/03/30
DOI:10.1039/C6CS00656F
Self-assembly, the autonomous organization of components to form patterns or structures, is a prevalent process in nature at all scales. Particularly, biological systems offer remarkable examples of diverse structures (as well as building blocks) and processes resulting from self-assembly. The exploration of bioinspired assemblies not only allows for mimicking the structures of living systems, but it also leads to functions for applications in different fields that benefit humans. In the last several decades, efforts on understanding and controlling self-assembly of small molecules have produced a large library of candidates for developing the biomedical applications of assemblies of small molecules. Moreover, recent findings in biology have provided new insights on the assemblies of small molecules to modulate essential cellular processes (such as apoptosis). These observations indicate that the self-assembly of small molecules, as multifaceted entities and processes to interact with multiple proteins, can have profound biological impacts on cells. In this review, we illustrate that the generation of assemblies of small molecules in cell milieu with their interactions with multiple cellular proteins for regulating cellular processes can result in primary phenotypes, thus providing a fundamentally new molecular approach for controlling cell behavior. By discussing the correlation between molecular assemblies in nature and the assemblies of small molecules in cell milieu, illustrating the functions of the assemblies of small molecules, and summarizing some guiding principles, we hope this review will stimulate more molecular scientists to explore the bioinspired self-assembly of small molecules in cell milieu.
Co-reporter:Yi Kuang, Yuan Gao, Junfeng Shi, Jie Li and Bing Xu
Chemical Communications 2014 - vol. 50(Issue 21) pp:NaN2774-2774
Publication Date(Web):2014/01/22
DOI:10.1039/C3CC48832B
The conjugation of taurine with a dipeptide derivative affords a cell compatible, small molecular hydrogelator to form hydrogels that exhibit rich phase transition behaviors in response to sonication and the change of pH or temperature.
Co-reporter:Zhaoqianqi Feng, Huaimin Wang, Xuewen Du, Junfeng Shi, Jie Li and Bing Xu
Chemical Communications 2016 - vol. 52(Issue 37) pp:NaN6335-6335
Publication Date(Web):2016/04/08
DOI:10.1039/C6CC02282K
Here we reported the first case in which enhancing self-assembling ability boosts anti-cancer efficacy through a simple and minimal modification of the C-terminus of a D-tripeptide. By only a 2% change of the molecular weight, this facile approach increases the inhibitory activity by over an order of magnitude (IC50 from 431 to 23 μM) towards an osteosarcoma cell line.
Co-reporter:Junfeng Shi, Xuewen Du, Dan Yuan, Richard Haburcak, Dongdong Wu, Ning Zhou and Bing Xu
Chemical Communications 2015 - vol. 51(Issue 23) pp:NaN4901-4901
Publication Date(Web):2015/02/12
DOI:10.1039/C4CC10374B
Enzymatic transformation is a fundamental process to control ligand–receptor interactions among proteins for signal transduction in cells. Here we report the first example of enzymatic transformation regulated ligand–receptor interactions of small molecules, in which enzymatic reaction changes the stoichiometry of the ligand–receptor binding from 1:1 to 1:2. We also show that this unique integration of enzymatic transformation and ligand–receptor interactions of small molecules is able to affect the fate of cells.
Co-reporter:Dongdong Wu, Jie Zhou, Junfeng Shi, Xuewen Du and Bing Xu
Chemical Communications 2014 - vol. 50(Issue 16) pp:NaN1994-1994
Publication Date(Web):2013/12/19
DOI:10.1039/C3CC48946A
Here we report the first example of a hydrogelator made of a conjugate of nucleobase–saccharide–amino acids by incorporating L-3-(2-naphthyl)-alanine to the conjugate, which illustrates a facile and effective method for generating bioactive and functional hydrogelators from the basic biological building blocks.
Co-reporter:Zhimou Yang, Yi Kuang, Xinming Li, Ning Zhou, Ye Zhang and Bing Xu
Chemical Communications 2012 - vol. 48(Issue 74) pp:NaN9259-9259
Publication Date(Web):2012/07/26
DOI:10.1039/C2CC34935C
As the first example of hydrogelator derived from aminoglycoside antibiotics, the hydrogel of kanamycin indicates that the hydrogel of aminoglycosides preserve the specific interaction with their macromolecular targets (e.g., 16S rRNA), thus illustrating a simple approach to explore and identify possible biological targets of supramolecular nanofibers/hydrogels.
Co-reporter:Bengang Xing, Tingting Jiang, Wuguo Bi, Yanmei Yang, Lihua Li, Manlun Ma, Chi-Kwong Chang, Bing Xu and Edwin Kok Lee Yeow
Chemical Communications 2011 - vol. 47(Issue 5) pp:NaN1603-1603
Publication Date(Web):2010/11/26
DOI:10.1039/C0CC04434B
A simple and specific divalent vancomycin–porphyrin has been developed. This divalent vancomycin–porphyrin conjugate indicates promising properties in fluorescent imaging and photodynamic inactivation of vancomycin-sensitive and vancomycin-resistant enterococci (VRE) bacterial strains.
Co-reporter:Yi Kuang, Yuan Gao, Junfeng Shi, Hsin-Chieh Lin and Bing Xu
Chemical Communications 2011 - vol. 47(Issue 31) pp:NaN8774-8774
Publication Date(Web):2011/06/24
DOI:10.1039/C1CC13115J
Imparting aromatic–aromatic interactions to the potassium binding epitope affords a supramolecular hydrogelator that responds to the K+ concentration by self-assembly into nanofibers of different widths and crosslinking patterns, which illustrates a simple approach to generate biomimic materials based on tunable, hierarchical self-assembly of small molecules.
Co-reporter:Yi Kuang, Yuan Gao and Bing Xu
Chemical Communications 2011 - vol. 47(Issue 47) pp:NaN12627-12627
Publication Date(Web):2011/10/31
DOI:10.1039/C1CC15577F
Consisting of N-terminated diphenylalanine, a new type of supramolecular hydrogelators forms hydrogels within a narrow pH window (pH 5.0 to 6.0) and selectively inhibits growth of HeLa cells, which provides important and useful insights for designing molecular nanofibers as potential nanomedicines.
Co-reporter:Xinming Li, Yuan Gao, Yi Kuang and Bing Xu
Chemical Communications 2010 - vol. 46(Issue 29) pp:NaN5366-5366
Publication Date(Web):2010/06/28
DOI:10.1039/C0CC00163E
This paper reports the first example of the use of an enzymatic reaction to generate a photoresponsive hydrogelator, which represents a convenient route to expand the scope of optically controlled molecular self-assembly in water.
Co-reporter:Yue Pan, Marcus J. C. Long, Hsin-Chieh Lin, Lizbeth Hedstrom and Bing Xu
Chemical Science (2010-Present) 2012 - vol. 3(Issue 12) pp:NaN3499-3499
Publication Date(Web):2012/09/10
DOI:10.1039/C2SC20519J
This work reports the first example of the biofunctional magnetic nanoparticles as a “magnetic dock” for directly sorting proteins inside live cells. We decorate the iron oxide nanoparticles with the ligands that bind selectively to fusion proteins consisting of the proteins of interest (POIs) and the ligand receptors. Similar to protein sorting processes on vesicles, the clusters of these functionalized magnetic nanoparticles only bind to the fusion proteins via the interaction with the receptors, but exhibit little interaction to other proteins. This work demonstrates new applications of magnetic nanoparticles and may ultimately contribute to the exploration of the functions of proteins via the selective, spatiotemporal control of the proteins by a magnetic force.
Co-reporter:Yue Pan, Marcus J. C. Long, Xinming Li, Junfeng Shi, Lizbeth Hedstrom and Bing Xu
Chemical Science (2010-Present) 2011 - vol. 2(Issue 5) pp:NaN948-948
Publication Date(Web):2011/03/03
DOI:10.1039/C1SC00030F
Iron oxide-based magnetic nanoparticles (MNP) surface-decorated with glutathione (GSH) via a dopamine anchor bind to human α1-glutathione S-transferase (GST) with high affinity and specificity and are able to separate GST fusion proteins from cell lysates. Both the purified GST and the protein of interest (POI) preserve their innate properties. The conjugate of MNP and the GST fusion protein also enables magnetic manipulation of cells.
Co-reporter:Fan Zhao, Man Lung Ma and Bing Xu
Chemical Society Reviews 2009 - vol. 38(Issue 4) pp:NaN891-891
Publication Date(Web):2009/02/12
DOI:10.1039/B806410P
This tutorial review aims to introduce a new kind of biomaterials—molecular hydrogels of therapeutic agents. Based on the molecular self-assembly in water, it is possible to transform therapeutic agents into analogues that form hydrogels without compromising their pharmacological efficacy. This transformation can be beneficial in three aspects: (i) the therapeutic agents become “self-deliverable” in the form of hydrogels; (ii) the self-assembly of hydrogelators of drugs might confer new and useful properties such as multivalency or high local densities; (iii) the exploration of molecular hydrogels of drugs may ultimately lead to bioactive molecules that have dual or multiple roles. By summarizing the reports on the molecular hydrogels made from clinical used drugs or other bioactive molecules, this article presents representative molecular hydrogels of therapeutics and outlines the promises and challenges for developing this new class of biomaterials.
Co-reporter:Dan Yuan, Junfeng Shi, Xuewen Du, Yibing Huang, Yuan Gao, Abdulgader A. Baoum and Bing Xu
Journal of Materials Chemistry A 2016 - vol. 4(Issue 7) pp:NaN1323-1323
Publication Date(Web):2016/01/11
DOI:10.1039/C5TB02346G
Based on the self-assembly capability of the core segment (GNNQQNY) of yeast prion Sup35, we design and synthesise a series of structurally related precursors for the enzymatic formation of hydrogels. We found that, with the catalysis of alkaline phosphatase, the precursor becomes a hydrogelator that self-assembles in water to form nanofibers with an average width less than ten nanometers. Interestingly, the introduction of an amyloid segment into a cytotoxic precursor (N′ffyp: D-1P) is able to abrogate the cytotoxicity of the precursor, making the resulting peptide cell compatible. This work contributes a new insight into the use of enzymes to form cell compatible hydrogels of peptide cross-β spine.
Co-reporter:Yue Pan, Yuan Gao, Junfeng Shi, Ling Wang and Bing Xu
Journal of Materials Chemistry A 2011 - vol. 21(Issue 19) pp:NaN6806-6806
Publication Date(Web):2011/04/04
DOI:10.1039/C1JM10822K
Here we report a novel supramolecular hydrogelator, which contains a nitrilotriacetic acid (NTA) motif, to form a magnetorheological hydrogel upon interacting with nickel particles or holmium ions or to afford a hydrogel as an efficient absorber of metal ions.
Co-reporter:Zhimou Yang, Ling Wang, Jingyu Wang, Ping Gao and Bing Xu
Journal of Materials Chemistry A 2010 - vol. 20(Issue 11) pp:NaN2132-2132
Publication Date(Web):2010/01/25
DOI:10.1039/B922858F
In this study, we report multi-component supramolecular hydrogels that exhibit exceptional high storage moduli and a rapid recovery of their original mechanical strength after removing external forces. The formation of such kind of supramolecular hydrogels is simple and versatile, and the components can be easily synthesized or commercially available in large quantities. The supramolecular hydrogels have been characterized by SEM and fluorescence spectrometry and the results obtained by both techniques correlate well with their mechanical properties. They have potential to be developed into useful materials that require high mechanical stiffness and possess rapid recovery properties, such as the injectable immobilization matrix for cells culture, drug release, enzyme encapsulation, etc.
Co-reporter:Fan Zhao, Balthasar A. Heesters, Isaac Chiu, Yuan Gao, Junfeng Shi, Ning Zhou, Michael C. Carroll and Bing Xu
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 35) pp:NaN6819-6819
Publication Date(Web):2014/07/23
DOI:10.1039/C4OB01362J
An L-rhamnose-based hydrogelator self-assembles to form nanofibrils, which, in contrast to the properties of monomeric L-rhamnose, suppress the antibody response of mice to phycoerythrin (PE), a fluorescent protein antigen. As the first example of the supramolecular assemblies of a saccharide to suppress immunity, this work illustrates a new approach of immunomodulation.
Co-reporter:Natsuko Yamagata, Xiaoyi Chen, Jie Zhou, Jie Li, Xuewen Du and Bing Xu
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 27) pp:NaN5692-5692
Publication Date(Web):2017/06/26
DOI:10.1039/C7OB01074E
Here we show the first example of an immunoreceptor tyrosine-based inhibitory motif (ITIM), LYYYYL, as well as its enantiomeric or retro-inverso peptide, to self-assemble in water via enzyme-instructed self-assembly. Upon enzymatic dephosphorylation, the phosphohexapeptides become hexapeptides, which self-assemble in water to result in supramolecular hydrogels. This work illustrates a new approach to design bioinspired soft materials from a less explored, but important pool of immunomodulatory peptides.
Co-reporter:Yuan Gao, Fan Zhao, Qigang Wang, Ye Zhang and Bing Xu
Chemical Society Reviews 2010 - vol. 39(Issue 9) pp:NaN3433-3433
Publication Date(Web):2010/07/12
DOI:10.1039/B919450A
Enzymes, together with the process of self-assembly, constitute necessary components of the foundation of life on the nanometre scale. The exceedingly high efficiency and selectivity exhibited by enzymes for catalyzing biotransformations naturally lead to the exploration of enzyme mimics and the applications of enzymes in industrial biotransformations. While the mimicking of enzymes aims to preserve the essence of enzymes in a simpler system than proteins, industrial biotransformations demand high activity and stability of enzymes. Recent research suggests that small peptide-based nanofibers in the form of molecular hydrogels can provide a general platform to achieve both important goals. This tutorial review will introduce the recent progress of these research activities on small peptide-based nanomaterials for catalysis and hopes to provide a starting point for further explorations that ultimately may lead to practical applications of enzymes and enzyme mimics for addressing important societal problems in energy, environment, and health.
Co-reporter:Yue Pan, Xuewen Du, Fan Zhao and Bing Xu
Chemical Society Reviews 2012 - vol. 41(Issue 7) pp:NaN2942-2942
Publication Date(Web):2012/02/08
DOI:10.1039/C2CS15315G
In the rapidly developing areas of nanobiotechnology, magnetic nanoparticles (MNPs) are one type of the most well-established nanomaterials because of their biocompatibility and the potential applications as alternative contrast enhancing agents for magnetic resonance imaging (MRI). While the development of MNPs as alternative contrast agents for MRI application has moved quickly to testing in animal models and clinical trials, other applications of biofunctional MNPs have been explored extensively at the stage of qualitative or conceptual demonstration. In this critical review, we summarize the development of two straightforward applications of biofunctional MNPs—manipulating proteins and manipulating cells—in the last five years or so and hope to provide a relatively comprehensive assessment that may help the future developments. Specifically, we start with the examination of the strategy for the surface functionalization of MNPs because the applications of MNPs essentially depend on the molecular interactions between the functional molecules on the MNPs and the intended biological targets. Then, we discuss the use of MNPs for manipulating proteins since protein interactions are critical for biological functions. Afterwards, we evaluate the development of the use of MNPs to manipulate cells because the response of MNPs to a magnetic field offers a unique way to modulate cellular behavior in a non-contact or “remote” mode (i.e. the magnet exerts force on the cells without direct contact). Finally, we provide a perspective on the future directions and challenges in the development of MNPs for these two applications. By reviewing the examples of the design and applications of biofunctional MNPs, we hope that this article will provide a reference point for the future development of MNPs that address the present challenges and lead to new opportunities in nanomedicine and nanobiotechnology (137 references).
Co-reporter:Yuan Gao, Marcus J. C. Long, Junfeng Shi, Lizbeth Hedstrom and Bing Xu
Chemical Communications 2012 - vol. 48(Issue 67) pp:NaN8406-8406
Publication Date(Web):2012/07/03
DOI:10.1039/C2CC33631F
Here we report the first example of the use of supramolecular hydrogels to discover the protein targets of aggregates of small molecules.
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