Co-reporter:Fei-He Ma, Yingli An, Jianzu Wang, Yiqing Song, Yang Liu, and Linqi Shi
ACS Nano October 24, 2017 Volume 11(Issue 10) pp:10549-10549
Publication Date(Web):October 2, 2017
DOI:10.1021/acsnano.7b05947
The folding process of a protein is inherently error-prone, owing to the large number of possible conformations that a protein chain can adopt. Partially folded or misfolded proteins typically expose hydrophobic surfaces and tend to form dysfunctional protein aggregates. Therefore, materials that can stabilize unfolded proteins and then efficiently assist them refolding to its bioactive form are of significant interest. Inspired by natural chaperonins, we have synthesized a series of polymeric nanochaperones that can facilitate the refolding of denatured proteins with a high recovery efficiency (up to 97%). Such nanochaperones possess phase-separated structure with hydrophobic microdomains on the surface. This structure allows nanochaperones to stabilize denatured proteins by binding them to the hydrophobic microdomains. We have also investigated the mechanism by which nanochaperones assist the protein refolding and established the design principles of nanochaperones in order to achieve effective recovery of a certain protein from their denatured forms. With a carefully designed composition of the microdomains according to the surface properties of the client proteins, the binding affinity between the hydrophobic microdomain and the denatured protein molecules can be tuned precisely, which enables the self-sorting of the polypeptides and the refolding of the proteins into their bioactive states. This work provides a feasible and effective strategy to recover inclusion bodies to their bioactive forms, which has potential to reduce the cost of the manufacture of recombinant proteins significantly.Keywords: inclusion body; molecular chaperone; nanochaperone; protein refolding; self-assembly;
Co-reporter:Fan Huang, Yang Gao, Yumin Zhang, Tangjian Cheng, Hanlin Ou, Lijun Yang, Jinjian Liu, Linqi Shi, and Jianfeng Liu
ACS Applied Materials & Interfaces May 24, 2017 Volume 9(Issue 20) pp:16880-16880
Publication Date(Web):May 8, 2017
DOI:10.1021/acsami.7b03347
Because of the mounting prevalence of complicated infections induced by multidrug-resistant bacteria, it is imperative to develop innovative and efficient antibacterial agents. In this work, we design a novel polymeric micelle for simultaneous decorating of silver nanoparticles and encapsulating of curcumin as a combination strategy to improve the antibacterial efficiency. In the constructed combination system, silver nanoparticles were decorated in the micellar shell because of the in situ reduction of silver ions, which were absorbed by the poly(aspartic acid) (PAsp) chains in the shell. Meanwhile, natural curcumin was encapsulated into the poly(ε-caprolactone) (PCL) core of the micelle through hydrophobic interaction. This strategy could prevent aggregation of silver nanoparticles and improve the water solubility of curcumin at the same time, which showed enhanced antibacterial activity toward Gram-negative P.aeruginosa and Gram-positive S.aureus compared with sliver-decorated micelle and curcumin-loaded micelle alone, due to the cooperative antibacterial effects of the silver nanoparticles and curcumin. Furthermore, the achieved combinational micelles had good biocompatibility and low hemolytic activity. Thus, our study provides a new pathway in the rational design of combination strategy for efficiently preventing the ubiquitous bacterial infections.Keywords: antibacterial; combination therapy; curcumin; polymeric micelle; silver nanoparticle;
Co-reporter:Lizhi Zhao, Ang Li, Rui Xiang, Liangliang Shen, and Linqi Shi
Langmuir July 16, 2013 Volume 29(Issue 28) pp:8936-8943
Publication Date(Web):July 16, 2013
DOI:10.1021/la401805x
Aggregation of FeIII-tetra-(4-sulfonatophenyl)-porphyrin (FeIIITPPS) was studied in the presence of block copolymers, poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP), poly(ethylene glycol)-block-poly(2-(dimethylamino)ethyl methylacrylate) (PEG-b-PDMAEMA), and poly(ethylene glycol)-block-poly(β-cyclodextrin) (PEG-b-PCD). The interaction between the iron porphyrin and the blocks, P4VP, PDMAEMA, and PCD, led to the formation of copolymers/FeIIITPPS complex micelles with a PEG shell and determined the species of FeIIITPPS. The electrostatic interaction of protonated P4VP and PDMAEMA with FeIIITPPS remarkably decreased the apparent pKd of FeIIITPPS and led to a micellar μ-oxo dimer of the iron porphyrin. At pH above the pKa of P4VP, FeIIITPPS was kept inside the hydrophobic P4VP core and formed an encapsulated μ-oxo dimer. However, when above the pKa of PDMAEMA, FeIIITPPS escaped from the hydrophobic PDMAEMA core, existing as a free μ-oxo dimer. PCD caused the monomer of the porphyrin because of the inclusion complexation between the β-cyclodextrin residues and FeIIITPPS. The two micellar monomer species FeIIITPPS(H2O)2 and FeIIITPPS(OH) were obtained with an equilibrium pKa ∼ 6.4.
Co-reporter:Qian Tao, Ang Li, Zhenkun Zhang, Rujiang Ma, and Linqi Shi
ACS Biomaterials Science & Engineering December 11, 2017 Volume 3(Issue 12) pp:3141-3141
Publication Date(Web):November 28, 2017
DOI:10.1021/acsbiomaterials.7b00764
The inactivation of multimeric enzymes is a more complicated process compared with that of monomeric enzymes. Stabilization of multimeric enzymes is regarded as a challenge with practical values in enzyme technology. Temperature-sensitive copolymer chitosan-graft- poly(N-isopropylacrylamide) was synthesized and encapsulated with multimeric enzymes in the confined spaces constructed by the W/O microemulsion. In this way, the quaternary structures of multimeric enzymes are stabilized and the thermal stabilities of them are enhanced. The whole process was studied and discussed. This method, which works well for both glucose oxidase and catalase, can be developed as a general protection strategy for multimeric enzymes.Keywords: confined space; multimeric enzyme; reversible thermoresponse; thermal stability;
Co-reporter:Rujiang Ma;Chuan Zhang;Yong Liu;Chang Li;Yanling Xu;Baoxin Li;Yunliang Zhang;Yingli An
RSC Advances (2011-Present) 2017 vol. 7(Issue 34) pp:21328-21335
Publication Date(Web):2017/04/10
DOI:10.1039/C7RA01742A
Amphiphilic block copolymer micelles in aqueous solution have been used extensively in delivery of hydrophobic drugs with the hydrophobic core serving as the reservoir. However, encapsulation of hydrophilic drugs by polymeric micelles with hydrophobic core is relatively difficult because of the poor interaction between them. Herein, we report a novel kind of pH/GSH dual-responsive complex micelles with a hydrophilic drug loaded, via direct subcomponent self-assembly of block copolymer poly(ethyleneglycol)-block-poly(L-lysine) (PEG-b-PLys), 2-formylbenzeneboronic acid (2-FPBA) and hydrophilic 1,2-diol-containing drugs (e.g. capecitabine (CAPE)) under physiological pH 7.4 based on the synergistic formation of an iminoboronate structure. The PEG-b-PLys/2-FPBA micelles without CAPE are well-characterized in terms of micellization mechanism, size, morphology, pH- and GSH-responsiveness. Encapsulation of CAPE by forming PEG-b-PLys/2-FPBA/CAPE complex micelles via synergistic formation of the iminoboronate structure is discussed and pH- and GSH-responsive drug-release studies are carried out. The complex micelles are stable under physiological neutral conditions but could be destroyed in response to the stimuli of physiological acidic condition (pH 5.0) and/or glutathione (GSH) at pH 7.4. pH- and GSH-responsive drug-releases are successfully achieved. The drug-loaded complex micelles could be endocytosed by HepG2 cells and efficiently deliver hydrophilic drugs into them. This type of complex micelles could be used as a promising platform for the delivery of hydrophilic 1,2-diol-containing drugs.
Co-reporter:Ruolin Wang;Rui Qu;Chen Jing;Yan Zhai;Yingli An
RSC Advances (2011-Present) 2017 vol. 7(Issue 17) pp:10100-10107
Publication Date(Web):2017/02/03
DOI:10.1039/C7RA00196G
Inspired by the structures of antenna-reaction centers in photosynthesis, a complex micelle was prepared from zinc tetrakis(4-sulfonatophenyl) porphyrin (ZnTPPS), modified fullerene (mC60) and poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys) by electrostatic interactions. The core–shell structure made the donor–acceptor system work in an aqueous environment. In the micellar core, ZnTPPS and mC60 molecules were surrounded by each other which ensured effective energy migration from the donor to the acceptor. The emission of the porphyrin was quenched efficiently which was confirmed by a series of fluorescence spectra. In comparison with the ZnTPPS micelle, the interaction of the mC60 with the porphyrin inhibited the generation of singlet oxygen, which was measured by electron paramagnetic resonance (EPR) and iodide method. In addition, enhanced generation of the superoxide radical was detected by reduction of nitro blue tetrazolium (NBT) in the presence of an electron donor. What is more, the complex micelle exhibited high electron transfer performance in the photocatalytic reduction of methyl viologen. The complex micellar structure endowed the donor–acceptor system with improved stability in an acidic environment. This strategy would be helpful for designing a new electron transfer platform and artificial photosynthetic system.
Co-reporter:Rui Qu;Hejin Shi;Ruolin Wang;Tangjian Cheng;Rujiang Ma;Yingli An
Biomaterials Science (2013-Present) 2017 vol. 5(Issue 3) pp:570-577
Publication Date(Web):2017/02/28
DOI:10.1039/C6BM00813E
Artificial enzymes are widely investigated to mimic the active center and the recognition center of natural enzymes. The active center is responsible for the catalytic activity of enzymes, and the recognition center provides enzymes with specificity. Most of the previous studies on artificial enzymes preferred to solve the problem of activity rather than specificity due to the complexity of the enzyme structures related to substrate recognition. Inspired by the multilevel structures of enzymes and the unique net-structures of hydrogels, hemin-micelles immobilized in alginate hydrogels (HM-AH) were constructed by multistep self-assembly. The hemin-micelle was the active center and mimicked the microenvironment of the catalytic site in horseradish peroxidase (HRP). The alginate hydrogel further enhanced the catalytic activity and stability of hemin-micelles and endowed the artificial enzymes with a catalytic capability in harsh water conditions and non-polar organic solvents. The hydrogel also served as the recognition center, which exhibited substrate selectivity owing to the diffusivity differentiations of substrates in hydrogel fibers. It is the first example of constructing a micelle-hydrogel complex system as an artificial enzyme with both catalytic activity and substrate selectivity by the method of multistep self-assembly.
Co-reporter:Ruo-lin Wang;Rui Qu;Yan Zhai;Chen Jing;Ang Li
Chinese Journal of Polymer Science 2017 Volume 35( Issue 11) pp:1328-1341
Publication Date(Web):29 August 2017
DOI:10.1007/s10118-017-1973-y
Inspired by structures of antenna-reaction centers in photosynthesis, the complex micelle was prepared from zinc tetra-phenyl porphyrin (ZnTPP), fullerene derivative (PyC60) and poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL). The core-shell structure made the hydrophobic donor-acceptor system work in aqueous. In micellar core, coordination interaction occurred between ZnTPP and PyC60 molecules which ensured the enhanced energy migration from the donor to the acceptor. The enhanced interaction between porphyrin and fullerene was confirmed by absorption, steady-state fluorescence and transient fluorescence. The generation of singlet oxygen and superoxide radical was detected by iodide method and reduction of nitro blue tetrazolium, respectively, which confirmed that electron transfer reaction in the complex micellar core occurred. Moreover, the complex micelle exhibited effective electron transfer performance in photodebromination of 2,3-dibromo-3-phenylpropionic acid. The complex micellar structure endowed the donor-acceptor system with improved stability under irradiation. This strategy could be helpful for designing new electron transfer platform and artificial photosynthetic system.
Co-reporter:Aoting Qu;Fan Huang;Ang Li;Huiru Yang;Hao Zhou;Jiafu Long
Chemical Communications 2017 vol. 53(Issue 7) pp:1289-1292
Publication Date(Web):2017/01/19
DOI:10.1039/C6CC07803F
By combining KLVFF peptide and self-assembly chaperone we fabricate a new system to achieve the synchronization between Aβ fibril disaggregation and reducing toxicity of Aβ fragments (monomers or oligomers) that consequently formed. When the KLVFF peptides disaggregate fibrils into fragments, the hydrophobic domains of self-assembly chaperones promptly bind them at the same time. This binding blocks the re-aggregation of the fragments and their interaction with cells, and hence reduces the toxicity of these dangerous fragments.
Co-reporter:Fan Huang, Liangliang Shen, Jianzu Wang, Aoting Qu, Huiru Yang, Zhenkun Zhang, Yingli An, and Linqi Shi
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 6) pp:3669
Publication Date(Web):November 16, 2015
DOI:10.1021/acsami.5b08843
Artificial chaperones are of great interest in fighting protein misfolding and aggregation for the protection of protein bioactivity. A comprehensive understanding of the interaction between artificial chaperones and proteins is critical for the effective utilization of these materials in biomedicine. In this work, we fabricated three kinds of artificial chaperones with different surface charges based on mixed-shell polymeric micelles (MSPMs), and investigated their protective effect for lysozymes under thermal stress. It was found that MSPMs with different surface charges showed distinct chaperone-like behavior, and the neutral MSPM with PEG shell and PMEO2MA hydrophobic domain at high temperature is superior to the negatively and positively charged one, because of the excessive electrostatic interactions between the protein and charged MSPMs. The results may benefit to optimize this kind of artificial chaperone with enhanced properties and expand their application in the future.Keywords: artificial chaperones; mixed-shell polymeric micelle; protein folding; self-assembly; surface charge
Co-reporter:Liping Chu, Honglin Gao, Tangjian Cheng, Yumin Zhang, Jinjian Liu, Fan Huang, Cuihong Yang, Linqi Shi and Jianfeng Liu
Chemical Communications 2016 vol. 52(Issue 37) pp:6265-6268
Publication Date(Web):04 Apr 2016
DOI:10.1039/C6CC01269H
Herein we report on a charge-adaptive nanosystem for prolonged and enhanced in vivo antibiotic delivery. The nanocarrier achieves acid-dependent charge conversion, thus prolonging the circulation time and enhancing antibiotic accumulation in subcutaneous inflammation models.
Co-reporter:Liangliang Shen, Rui Qu, Hejin Shi, Fan Huang, Yingli An and Linqi Shi
Biomaterials Science 2016 vol. 4(Issue 5) pp:857-862
Publication Date(Web):24 Mar 2016
DOI:10.1039/C6BM00046K
Herein, a complex micelle as an oxygen nano-carrier is constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys), tetrakis(4-sulfonatophenyl)porphinato cobalt(II) (Co(II)TPPS), a heptapeptide (Cys-His-His-His-His-His-His) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD). Co(II)TPPS was encapsulated into the cavities of TM-β-CDs driven by the host–guest interaction so that the irreversible formation of a μ-oxo-dimer of Co(II)TPPS can be effectively prevented. The imidazole groups of the heptapeptide were selected as good axial ligands coordinating to the centric cobalt of Co(II)TPPS, which subtly constituted the five-coordinated precursor serving as an active functional centre for oxygen binding. The sixth position of Co(II)TPPS can bind oxygen. Furthermore, the host–guest inclusion (TM-β-CD/Co(II)TPPS) was loaded into the hydrophobic core of the complex micelle and tightly fixed with PLys chains. The hydrophilic PEG blocks stretched in the aqueous solution constitute the shells which stabilize the structure of the complex micelle as well as impart the complex micelle sufficient blood circulation time. Moreover, the complex micelle exhibited excellent biocompatibility and cellular uptake. Therefore, the rationally designed amphiphilic structure can work as promising artificial O2 carriers in vivo. Potentially, the complex micelle can be expected to change the anaerobic microenvironment and find applications in the repair of the cells damaged by cellular hypoxia.
Co-reporter:Jianzu Wang, Yiqing Song, Pingchuan Sun, Yingli An, Zhenkun Zhang, and Linqi Shi
Langmuir 2016 Volume 32(Issue 11) pp:2737-2749
Publication Date(Web):March 5, 2016
DOI:10.1021/acs.langmuir.6b00356
Molecular chaperones can elegantly fine-tune its hydrophobic/hydrophilic balance to assist a broad spectrum of nascent polypeptide chains to fold properly. Such precious property is difficult to be achieved by chaperone mimicking materials due to limited control of their surface characteristics that dictate interactions with unfolded protein intermediates. Mixed shell polymeric micelles (MSPMs), which consist of two kinds of dissimilar polymeric chains in the micellar shell, offer a convenient way to fine-tune surface properties of polymeric nanoparticles. In the current work, we have fabricated ca. 30 kinds of MSPMs with finely tunable hydrophilic/hydrophobic surface properties. We investigated the respective roles of thermosensitive and hydrophilic polymeric chains in the thermodenaturation protection of proteins down to the molecular structure. Although the three kinds of thermosensitive polymers investigated herein can form collapsed hydrophobic domains on the micellar surface, we found distinct capability to capture and release unfolded protein intermediates, due to their respective affinity for proteins. Meanwhile, in terms of the hydrophilic polymeric chains in the micellar shell, poly(ethylene glycol) (PEG) excels in assisting unfolded protein intermediates to refold properly via interacting with the refolding intermediates, resulting in enhanced chaperone efficiency. However, another hydrophilic polymer-poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) severely deteriorates the chaperone efficiency of MSPMs, due to its protein-resistant properties. Judicious combination of thermosensitive and hydrophilic chains in the micellar shell lead to MSPM-based artificial chaperones with optimal efficacy.
Co-reporter:Yong Liu, Henk J. Busscher, Bingran Zhao, Yuanfeng Li, Zhenkun Zhang, Henny C. van der Mei, Yijin Ren, and Linqi Shi
ACS Nano 2016 Volume 10(Issue 4) pp:4779
Publication Date(Web):March 21, 2016
DOI:10.1021/acsnano.6b01370
Biofilms cause persistent bacterial infections and are extremely recalcitrant to antimicrobials, due in part to reduced penetration of antimicrobials into biofilms that allows bacteria residing in the depth of a biofilm to survive antimicrobial treatment. Here, we describe the preparation of surface-adaptive, Triclosan-loaded micellar nanocarriers showing (1) enhanced biofilm penetration and accumulation, (2) electrostatic targeting at acidic pH toward negatively charged bacterial cell surfaces in a biofilm, and (3) antimicrobial release due to degradation of the micelle core by bacterial lipases. First, it was established that mixed-shell-polymeric-micelles (MSPM) consisting of a hydrophilic poly(ethylene glycol) (PEG)-shell and pH-responsive poly(β-amino ester) become positively charged at pH 5.0, while being negatively charged at physiological pH. This is opposite to single-shell-polymeric-micelles (SSPM) possessing only a PEG-shell and remaining negatively charged at pH 5.0. The stealth properties of the PEG-shell combined with its surface-adaptive charge allow MSPMs to penetrate and accumulate in staphylococcal biofilms, as demonstrated for fluorescent Nile red loaded micelles using confocal-laser-scanning-microscopy. SSPMs, not adapting a positive charge at pH 5.0, could not be demonstrated to penetrate and accumulate in a biofilm. Once micellar nanocarriers are bound to a staphylococcal cell surface, bacterial enzymes degrade the MSPM core to release its antimicrobial content and kill bacteria over the depth of a biofilm. This constitutes a highly effective pathway to control blood-accessible staphylococcal biofilms using antimicrobials, bypassing biofilm recalcitrance to antimicrobial penetration.Keywords: antimicrobials; biofilm; electrostatic interactions; micelles; pH-responsiveness; staphylococci; Triclosan
Co-reporter:Sheng Liang;Yang Liu;Xin Jin;Gan Liu;Jing Wen;Linlin Zhang;Jie Li
Nano Research 2016 Volume 9( Issue 4) pp:1022-1031
Publication Date(Web):2016 April
DOI:10.1007/s12274-016-0991-3
Protein therapy, wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparticles in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.
Co-reporter:Tangjian Cheng, Rujiang Ma, Yumin Zhang, Yuxun Ding, Jinjian Liu, Hanlin Ou, Yingli An, Jianfeng Liu and Linqi Shi
Chemical Communications 2015 vol. 51(Issue 81) pp:14985-14988
Publication Date(Web):11 Aug 2015
DOI:10.1039/C5CC05854F
Based on the protonation/deprotonation of poly(β-amino ester) (PAE), mixed-shell micelles (MSMs) with adaptive surfaces could rapidly and reversibly change surface properties to prolong circulation time in blood (pH 7.4) and enhance cellular uptake at tumor sites (pH 6.5).
Co-reporter:Jianzu Wang, Tao Yin, Fan Huang, Yiqing Song, Yingli An, Zhenkun Zhang, and Linqi Shi
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 19) pp:10238
Publication Date(Web):May 4, 2015
DOI:10.1021/acsami.5b00684
Controlled and reversible interactions between polymeric nanoparticles and proteins have gained more and more attention with the hope to address many biological issues such as prevention of protein denaturation, interference of the fibrillation of disease relative proteins, removing of toxic biomolecules as well as targeting delivery of proteins, etc. In such cases, proper analytic techniques are needed to reveal the underlying mechanism of the particle-protein interactions. In the current work, Förster Resonance Energy Transfer (FRET) was used to investigate the interaction of our tailor designed artificial chaperone based on mixed shell polymeric micelles (MSPMs) with their substrate proteins. We designed a new kind of MSPMs with fluorescent acceptors precisely placed at the desired locations as well as hydrophobic domains which can adsorb unfolded proteins with a propensity to aggregate. Interactions of such model micelles with a donor-labeled protein-FITC-lysozyme, was monitored by FRET. The fabrication strategy of MSPMs makes it possible to control the accurate location of the acceptor, which is critical to reveal some unexpected insights of the micelle-protein interactions upon heating and cooling. Preadsorption of native proteins onto the hydrophobic domains of the MSPMs is a key step to prevent thermo-denaturation by diminishing interprotein aggregations. Reversible protein adsorption during heating and releasing during cooling have been confirmed. Conclusions from the FRET effect are in line with the measurement of residual enzymatic activity.Keywords: artificial chaperone; Förster resonance energy transfer; mixed shell polymeric micelle; nanoparticle; protein;
Co-reporter:Rui Qu, Liangliang Shen, Aoting Qu, Ruolin Wang, Yingli An, and Linqi Shi
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 30) pp:16694
Publication Date(Web):July 15, 2015
DOI:10.1021/acsami.5b04398
Inspired by delicate structures and multiple functions of natural multiple enzyme architectures such as peroxisomes, we constructed an artificial multiple enzyme system by coencapsulation of glucose oxidases (GOx) and artificial peroxidases in a supramolecular hydrogel. The artificial peroxidase was a functional complex micelle, which was prepared by the self-assembly of diblock copolymer and hemin. Compared with catalase or horseradish peroxidase (HRP), the functional micelle exhibited comparable activity and better stability, which provided more advantages in constructing a multienzyme with a proper oxidase. The hydrogel containing the two catalytic centers was further used as a catalyst for green oxidation of glucose, which was a typical cascade reaction. Glucose was oxidized by oxygen (O2) via the GOx-mediated reaction, producing toxic intermediate hydrogen peroxide (H2O2). The produced H2O2 further oxidized peroxidase substrates catalyzed by hemin-micelles. By regulating the diffusion modes of the enzymes and substrates, the artificial multienzyme based on hydrogel could successfully activate the cascade reaction, which the soluble enzyme mixture could not achieve. The hydrogel, just like a protective covering, protected oxidases and micelles from inactivation via toxic intermediates and environmental changes. The artificial multienzyme could efficiently achieve the oxidation task along with effectively eliminating the toxic intermediates. In this way, this system possesses great potentials for glucose detection and green oxidation of a series of substrates related to biological processes.Keywords: artificial peroxidase; cascade reaction; multiple enzyme system; oxidase; self-assembly
Co-reporter:Hao Yang, Rujiang Ma, Jing Yue, Chang Li, Yong Liu, Yingli An and Linqi Shi
Polymer Chemistry 2015 vol. 6(Issue 20) pp:3837-3846
Publication Date(Web):07 Apr 2015
DOI:10.1039/C5PY00170F
A facile strategy toward the construction of glucose-responsive polymer vesicles at physiological pH is reported. A thermo-sensitive phenylboronic acid (PBA)-containing block copolymer PNIPAM-b-P(Asp-co-AspPBA) was self-assembled into core–shell (CS) micelles with a PNIPAM core and a P(Asp-co-AspPBA) shell above the LCST of PNIPAM. The addition of a glucosamine (GA)-containing block copolymer PEG-b-P(Asp-co-AspGA) resulted in the formation of core–shell–corona (CSC) complex micelles because of the crosslinking between PBA- and GA-containing blocks. Polymer vesicles with a swollen PNIPAM core, a cross-linked P(Asp-co-AspPBA)/P(Asp-co-AspGA) vesicular membrane, and a PEG corona were obtained simply by storing the CSC complex micelles below the LCST of PNIPAM. A combination of transmission electron microscopy (TEM) and dynamic light scattering (DLS) in terms of the variations of hydrodynamic diameter (Dh) and light scattering intensity (LSI) was applied to characterize the polymer vesicles in PBS solution with glucose. The polymer vesicles had a hydrophilic vesicular membrane which was favorable for the penetration of water-soluble substances and exhibited prominent glucose-responsiveness at physiological pH 7.4. FITC-insulin as a model protein was encapsulated in the polymer vesicles and the glucose-triggered insulin release was investigated.
Co-reporter:Tao Yin, Xue Liu, Jianzu Wang, Yingli An, Zhenkun Zhang and Linqi Shi
RSC Advances 2015 vol. 5(Issue 59) pp:47458-47465
Publication Date(Web):08 May 2015
DOI:10.1039/C5RA06021D
Hybrid particulate composites consisting of noble metal nanoparticles (NPs) and polymeric particles have attracted intensive interest, due to the possibility of combining the precious optical and catalytic properties of the former with the stimuli responsiveness and biocompatibility of the latter. However, it is challenging to prepare hybrid particles that simultaneously have tunable optical and catalytic properties as well as excellent colloidal stability. In the current work, we report a strategy for such hybrid particles, through covalently decorating the outmost surface of mixed shell polymeric micelles (MSPMs) with gold NPs. For this, two block polymers, poly(ε-caprolactone)-block-(ethylene glycol) (PCL-b-PEG) and poly(ε-caprolactone)-block-poly(N-isopropylacrylamide) (PCL-b-PNIPAM), were prepared by ring-opening polymerization and reversible addition fragmentation chain transfer (RAFT) polymerization, respectively. Co-self-assembly of the two block polymers result in MSPMs with a PCL core and a mixed shell consisting of PEG and PNIPAM. At the end of each PNIPAM chain in the shell, thiol groups are introduced to act as anchors for the in situ formation of gold NPs. The number density of the gold NPs is conveniently tuned through varying the relative amount of PEG/PNIPAM in the micellar shell. Reversible shrinking and extension of the PNIPAM chains regulated by temperature can be used to tune the interparticle distance of the gold NPs, while the whole hybrid particles are stabilized by the stretched PEG chains. The hybrid polymeric micelles exhibit thermoresponsive surface plasmon resonance and enhanced catalytic properties as well as excellent colloidal stability.
Co-reporter:Hao Yang, Chuan Zhang, Chang Li, Yong Liu, Yingli An, Rujiang Ma, and Linqi Shi
Biomacromolecules 2015 Volume 16(Issue 4) pp:
Publication Date(Web):March 24, 2015
DOI:10.1021/acs.biomac.5b00155
Polymeric nanoparticles with glucose-responsiveness are of great interest in developing a self-regulated drug delivery system. In this work, glucose-responsive polymer vesicles were fabricated based on the complexation between a glucosamine (GA)-containing block copolymer PEG45-b-P(Asp-co-AspGA) and a phenylboronic acid (PBA)-containing block copolymer PEG114-b-P(Asp-co-AspPBA) with α-CD/PEG45 inclusion complex as the sacrificial template. The obtained polymer vesicles composed of cross-linked P(Asp-co-AspGA)/P(Asp-co-AspPBA) layer as wall and PEG chains as both inner and outer coronas. The vesicular morphology was observed by transmission electron microscopy (TEM), and the glucose-responsiveness was investigated by monitoring the variations of hydrodynamic diameter (Dh) and light scattering intensity (LSI) in the polymer vesicle solution with glucose using dynamic light scattering (DLS). Vancomycin as a model drug was encapsulated in the polymer vesicles and sugar-triggered drug release was carried out. This kind of polymer vesicle may be a promising candidate for glucose-responsive drug delivery.
Co-reporter:Liangliang Shen;Lizhi Zhao;Rui Qu;Fan Huang;Hongjun Gao;Yingli An
Nano Research 2015 Volume 8( Issue 2) pp:491-501
Publication Date(Web):2015 February
DOI:10.1007/s12274-014-0651-4
A complex micelle as a hemoglobin functional model with the biaoactive function of reversible oxygen transfer has been constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-blockpoly(4-vinylpyridine-co-N-heptyl-4-vinylpyridine) (PEG-b-P(4VP-co-4VPHep)), tetrakis(4-sulfonatophenyl)porphinato iron(II) (Fe(II)TPPS) and β-cyclodextrin (β-CD). The μ-oxo dimer of Fe(II)TPPS was successfully inhibited because the Fe(II)TPPS was included into the cavities of β-CDs through host-guest interaction. Fe(II)TPPS coordinated with pyridine groups functions as the active site to reversibly bind dioxygen. In adition, the host-guest inclusion (β-CD/Fe(II)TPPS) was encapsulated in the hydrophobic core of the complex micelle and tightly fixed by P4VP chains. The hydrophilic PEG blocks stretched in aqueous solution to constitute the shells which stabilize the structure of the complex micelle as well as endow the complex micelle with sufficient blood circulation time. Dioxygen can be bound to the Fe(II)TPPS located in the confined space and excellent reversibility of the binding-release process of dioxygen can be achieved. The quaternary amine N-heptyl-4-vinylpyridine can coerce abundant S2O42− ions into the core of the complex micelle to facilitate the self-reduction process. Dioxygen adducts (Fe(II)TPPS(O2)) were effectively protected by the double hydrophobic barriers constructed by the cavity of the cyclodextrin and the core of the complex micelle which enhances the ability to resist nucleophilic molecules. Therefore, the rationally designed amphiphilic structure can work as a promising artificial O2 carrier. Potentially, the complex micelle can be expected to improve the treatment of diseases linked with hypoxia.
Co-reporter:Zhenkun Zhang, Rujiang Ma, and Linqi Shi
Accounts of Chemical Research 2014 Volume 47(Issue 4) pp:1426
Publication Date(Web):April 2, 2014
DOI:10.1021/ar5000264
In the past decades, polymer based nanoscale polymeric assemblies have attracted continuous interest due to their potential applications in many fields, such as nanomedicine. Many efforts have been dedicated to tailoring the three-dimensional architecture and the placement of functional groups at well-defined positions within the polymeric assemblies, aiming to augment their function. To achieve such goals, in one way, novel polymeric building blocks can be designed by controlled living polymerization methodology and advanced chemical modifications. In contrast, by focusing on the end function, others and we have been practicing strategies of cooperative self-assembly of multiple polymeric building blocks chosen from the vast library of conventional block polymers which are easily available. The advantages of such strategies lie in the simplicity of the preparation process and versatile choice of the constituent polymers in terms of their chemical structure and functionality as well as the fact that cooperative self-assembly based on supramolecular interactions offers elegant and energy-efficient bottom-up strategies. Combination of these principles has been exploited to optimize the architecture of polymeric assemblies with improved function, to impart new functionality into micelles and to realize polymeric nanocomplexes exhibiting functional integration, similar to some natural systems like artificial viruses, molecular chaperones, multiple enzyme systems, and so forth.In this Account, we shall first summarize several straightforward designing principles with which cooperative assembly of multiple polymeric building blocks can be implemented, aiming to construct polymeric nanoassemblies with hierarchal structure and enhanced functionalities. Next, examples will be discussed to demonstrate the possibility to create multifunctional nanoparticles by combination of the designing principles and judiciously choosing of the building blocks. We focus on multifunctional nanoparticles which can partially address challenges widely existing in nanomedicine such as long blood circulation, efficient cellular uptake, and controllable release of payloads. Finally, bioactive polymeric assemblies, which have certain functions closely mimicking those of some natural systems, will be used to conceive the concept of functional integration.
Co-reporter:Rui Qu, Liangliang Shen, Zhihua Chai, Chen Jing, Yufeng Zhang, Yingli An, and Linqi Shi
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 21) pp:19207
Publication Date(Web):October 6, 2014
DOI:10.1021/am505232h
Following an inspiration from the fine structure of natural peroxidases, such as horseradish peroxidase (HRP), an artificial peroxidase was constructed through the self-assembly of diblock copolymers and hemin, which formed a functional micelle with peroxidase-like activity. The pyridine moiety in block copolymer poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP) can coordinate with hemin, and thus hemin is present in a five-coordinate complex with an open site for binding substrates, which mimics the microenvironment of heme in natural peroxidases. The amphiphilic core–shell structure of the micelle and the coordination interaction of the polymer to the hemin inhibit the formation of hemin μ-oxo dimers, and thereby enhance the stability of hemin in the water phase. Hemin-micelles exhibited excellent catalytic performance in the oxidation of phenolic and azo compounds by H2O2. In comparison with natural peroxidases, hemin-micelles have higher catalytic activity and better stability over wide temperature and pH ranges. Hemin-micelles can be used as a detection system for H2O2 with chromogenic substrates, and they anticipate the possibility of constructing new biocatalysts tailored to specific functions.Keywords: artificial peroxidase; block copolymer; coordination; hemin; micelle
Co-reporter:Rujiang Ma and Linqi Shi
Polymer Chemistry 2014 vol. 5(Issue 5) pp:1503-1518
Publication Date(Web):11 Oct 2013
DOI:10.1039/C3PY01202F
Glucose-responsive materials have attracted great intention in recent years due to their potential application in drug delivery. Phenylboronic acid-containing materials have been most widely studied and used in construction of glucose-responsive system for insulin delivery. This review covers the recent advances in synthesis of phenylboronic acid-based glucose-responsive materials, especially in forms of nanogels (microgels), micelles, vesicles, and mesoporous silica nanoparticles. Applications of these nanomaterials in drug delivery are discussed.
Co-reporter:Rujiang Ma;Beilei Wang;Pingchuan Sun
Chinese Journal of Chemistry 2014 Volume 32( Issue 1) pp:97-102
Publication Date(Web):
DOI:10.1002/cjoc.201300920
Abstract
Phenylboronic acid (PBA) based glucose-responsive materials have attracted great interests in recent years for developing insulin delivery systems. It is desired to obtain PBA based materials that can response to glucose under physiological pH and understand the mechanism. By using 11B triple-quantum magic-angle spinning nuclear magnetic resonance (11B 3Q MAS NMR) measurements, the glucose-responsive mechanism of micelles self-assembled from poly(ethylene glycol)-b-ploy(acrylic acid-co-acrylamidophenylboronic acid) PEG-b-P(AA-co-AAPBA) is deeply investigated. Different configurations of phenylboronic acid during various steps of glucose-responsive behaviors are clearly analyzed in the 11B 3Q MAS NMR spectra and coordination between carboxyl and PBA is confirmed. By increasing the AA units in PEG-b-P(AA-co-AAPBA), the carboxyl can coordinate with PBA moieties and cause the glucose-responsiveness of micelles even in the weak acid environment.
Co-reporter:Ang Li, Lizhi Zhao, Jing Hao, Rujiang Ma, Yingli An, and Linqi Shi
Langmuir 2014 Volume 30(Issue 16) pp:4797-4805
Publication Date(Web):2017-2-22
DOI:10.1021/la500252c
Complexation between 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLL) was performed via electrostatic interaction. Two kinds of primary arrays of TPPS with different supramolecular chirality induced by PLL were obtained in the resultant complex by inverting the mixing procedure of the two components. These arrays could be displaced by poly(sodium-p-styrenesulfonate) (PSS) from the chiral PLL template through competitive electrostatic complexation, and then PSS formed a polyion complex micelle with PEG-b-PLL. The template-removed TPPS arrays preserved their induced chirality and served as primary subunits for the secondary aggregation of TPPS. The morphology of the secondary aggregates was strongly dependent upon the asymmetric primary supramolecular arrangement of TPPS. The rodlike nanostructure that was ∼200 nm in length was composed of the primary arrays that showed opposite exciton chirality between the J- and H-bands. In contrast, the micrometer-sized fibrils observed were composed of the arrays with the same exciton chirality at the J- and H-bands.
Co-reporter:Fan Huang;Jianzu Wang;Aoting Qu;Liangliang Shen;Dr. Jinjian Liu;Jianfeng Liu;Dr. Zhenkun Zhang;Yingli An; Linqi Shi
Angewandte Chemie International Edition 2014 Volume 53( Issue 34) pp:8985-8990
Publication Date(Web):
DOI:10.1002/anie.201400735
Abstract
The disruption of Aβ homeostasis, which results in the accumulation of neurotoxic amyloids, is the fundamental cause of Alzheimer’s disease (AD). Molecular chaperones play a critical role in controlling undesired protein misfolding and maintaining intricate proteostasis in vivo. Inspired by a natural molecular chaperone, an artificial chaperone consisting of mixed-shell polymeric micelles (MSPMs) has been devised with tunable surface properties, serving as a suppressor of AD. Taking advantage of biocompatibility, selectivity toward aberrant proteins, and long blood circulation, these MSPM-based chaperones can maintain Aβ homeostasis by a combination of inhibiting Aβ fibrillation and facilitating Aβ aggregate clearance and simultaneously reducing Aβ-mediated neurotoxicity. The balance of hydrophilic/hydrophobic moieties on the surface of MSPMs is important for their enhanced therapeutic effect.
Co-reporter:Fan Huang;Jianzu Wang;Aoting Qu;Liangliang Shen;Dr. Jinjian Liu;Jianfeng Liu;Dr. Zhenkun Zhang;Yingli An; Linqi Shi
Angewandte Chemie 2014 Volume 126( Issue 34) pp:9131-9136
Publication Date(Web):
DOI:10.1002/ange.201400735
Abstract
The disruption of Aβ homeostasis, which results in the accumulation of neurotoxic amyloids, is the fundamental cause of Alzheimer’s disease (AD). Molecular chaperones play a critical role in controlling undesired protein misfolding and maintaining intricate proteostasis in vivo. Inspired by a natural molecular chaperone, an artificial chaperone consisting of mixed-shell polymeric micelles (MSPMs) has been devised with tunable surface properties, serving as a suppressor of AD. Taking advantage of biocompatibility, selectivity toward aberrant proteins, and long blood circulation, these MSPM-based chaperones can maintain Aβ homeostasis by a combination of inhibiting Aβ fibrillation and facilitating Aβ aggregate clearance and simultaneously reducing Aβ-mediated neurotoxicity. The balance of hydrophilic/hydrophobic moieties on the surface of MSPMs is important for their enhanced therapeutic effect.
Co-reporter:Zhihua Chai;Chen Jing;Yong Liu;Yingli An
Colloid and Polymer Science 2014 Volume 292( Issue 6) pp:1329-1337
Publication Date(Web):2014 June
DOI:10.1007/s00396-014-3186-z
Inspired by natural photosynthesis, we employed polymeric micelles to enhance the water solubility and photostability of hydrophobic metallo-tetraphenylporphyrin (metallo-TPP) by complexation with poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP) via axial coordination. The structure and photochemical properties of the complex micelles were characterized by UV-visible spectroscopy, fluorescence spectroscopy, and laser light scatting. The photostability and electron transfer ability of metalloporphyrins in the micelles were investigated under continuous irradiation. The results show that metallo-TPPs entrapped in the micellar cores possess higher photostability and better electron transfer ability. The hydrophobic metalloporphyrins remains active inside the micelles which is reminiscent of chlorophyll protein complex in photosynthesis. The use of micelle thus may provide a promising system on designing photocatalysts for targeting applications in solar energy conversion and photodynamic tumor therapy (PDT).
Co-reporter:Hongjun Gao, Tangjian Cheng, Jianfeng Liu, Jinjian Liu, Cuihong Yang, Liping Chu, Yumin Zhang, Rujiang Ma, and Linqi Shi
Biomacromolecules 2014 Volume 15(Issue 10) pp:
Publication Date(Web):August 22, 2014
DOI:10.1021/bm5009348
Exploring ideal nanocarriers for drug delivery systems has encountered unavoidable hurdles, especially the conflict between enhanced cellular uptake and prolonged blood circulation, which have determined the final efficacy of cancer therapy. Here, based on controlled self-assembly, surface structure variation in response to external environment was constructed toward overcoming the conflict. A novel micelle with mixed shell of hydrophilic poly(ethylene glycol) PEG and pH responsive hydrophobic poly(β-amino ester) (PAE) was designed through the self-assembly of diblock amphiphilic copolymers. To avoid the accelerated clearance from blood circulation caused by the surface exposed targeting group c(RGDfK), here c(RGDfK) was conjugated to the hydrophobic PAE and hidden in the shell of PEG at pH 7.4. At tumor pH, charge conversion occurred, and c(RGDfK) stretched out of the shell, leading to facilitated cellular internalization according to the HepG2 cell uptake experiments. Meanwhile, the heterogeneous surface structure endowed the micelle with prolonged blood circulation. With the self-regulated multifunctional collaborated properties of enhanced cellular uptake and prolonged blood circulation, successful inhibition of tumor growth was achieved from the demonstration in a tumor-bearing mice model. This novel nanocarrier could be a promising candidate in future clinical experiments.
Co-reporter:Hao Yang, Xiaocheng Sun, Gan Liu, Rujiang Ma, Zhong Li, Yingli An and Linqi Shi
Soft Matter 2013 vol. 9(Issue 35) pp:8589-8599
Publication Date(Web):11 Jul 2013
DOI:10.1039/C3SM51538A
Phenylboronic acid (PBA)-based polymers have attracted much attention because of their potential applications in glucose-responsive insulin delivery for the treatment of diabetes. Herein, we prepared a kind of glucose-responsive complex micelles by the complexation between a phenylboronic acid-containing block copolymer PEG-b-P(Asp-co-AspPBA) and a glycopolymer P(Asp-co-AGA). The complex micelles combined a variety of advantages such as stability against aggregation due to the PEG shell, fast response to glucose at neutral pH due to the complex core composed of two hydrophilic polymers, and more importantly better glucose sensitivity ascribed to the decreased apparent pKa of the PBA/AGA complex. Moreover, glucose-triggered on–off release of insulin was obtained under physiological pH 7.4 with 2 g L−1 glucose (hyperglycemia), which provided us with an effective strategy for self-regulated insulin delivery in response to physiological glucose level. The enhanced biocompatibility of this complex micelles system was confirmed by MTT assay. This type of complex micelles may be a promising candidate for in vivo insulin delivery.
Co-reporter:Gan Liu, Rujiang Ma, Jie Ren, Zhong Li, Haixia Zhang, Zhenkun Zhang, Yingli An and Linqi Shi
Soft Matter 2013 vol. 9(Issue 5) pp:1636-1644
Publication Date(Web):11 Dec 2012
DOI:10.1039/C2SM26690C
We developed a glucose-responsive complex polymeric micelle (CPM) through the self-assembly of two types of diblock copolymers, poly(ethylene glycol)-b-poly(aspartic acid-co-aspartamidophenylboronic acid) (PEG-b-P(Asp-co-AspPBA)) and poly(N-isopropylacrylamide)-b-poly(aspartic acid-co-aspartamidophenylboronic acid) (PNIPAM-b-P(Asp-co-AspPBA)). By controlling the weight ratio between PNIPAM and PEG (WPNIPAM/WPEG = 6/4), the block copolymers form complex micelles with a novel core–shell–corona structure. By following this structure, the continuous PNIPAM shell collapsed on the glucose-responsive P(Asp-co-AspPBA) core. As a result, the CPM exhibits a reversible swelling in response to changes in the glucose concentration, enabling the repeated on–off release of insulin regulated by glucose level. Furthermore, the CPM could effectively protect the encapsulated insulin against protease degradation. Therefore, this glucose-responsive CPM provides a simple and powerful strategy to construct a self-regulated insulin delivery system for diabetes treatment.
Co-reporter:Zhihua Chai, Hongjun Gao, Jie Ren, Yingli An and Linqi Shi
RSC Advances 2013 vol. 3(Issue 40) pp:18351-18358
Publication Date(Web):05 Aug 2013
DOI:10.1039/C3RA42616E
Inspired by the chlorophyll–protein complex in photosynthesis, two types of micelles were formed by the noncovalent complexes between magnesium porphyrins and block copolymers. A series of electrostatic micelles were prepared from magnesium tetrakis(4-sulfonatophenyl) porphyrin (MgTPPS) and poly(ethylene glycol)-block-poly(L-lysine). Meanwhile, the coordination micelles were fabricated from MgTPPS and poly(ethylene glycol)-block-poly(4-vinylpyridine). Here, we aim to analyze the origin of the enhanced stability of MgTPPS, particularly focusing on the photoactivity of MgTPPS in the micelles. The electrostatic micelles had better hydrolytic stability due to the electrostatic repulsion interaction and the coordination micelles showed high photostability, benefiting from axial coordination. The electrostatic micelles can promote the generation of singlet oxygen due to their swollen micellar cores. While the coordination micelles displayed better electron transfer ability owing to the lower HOMO of MgTPPS induced by axial coordination. These results may provide a novel approach to understand the amazing properties of the natural chlorophyll–protein complex and also have important implications, such as, in artificial photosynthetic reactions and photodynamic therapy.
Co-reporter:Hongjun Gao, Jie Xiong, Tangjian Cheng, Jinjian Liu, Liping Chu, Jianfeng Liu, Rujiang Ma, and Linqi Shi
Biomacromolecules 2013 Volume 14(Issue 2) pp:
Publication Date(Web):January 2, 2013
DOI:10.1021/bm301694t
The miserable targeting performance of nanocarriers for cancer therapy arises largely from the rapid clearance from blood circulation and the major accumulation in the organs of the reticuloendothelial system (RES), leading to inefficient enhanced permeability and retention (EPR) effect after intravenous injection (i.v.). Herein, we reported an efficient method to prolong the blood circulation of nanoparticles and decrease their deposition in liver and spleen. In this work, we fabricated a series of mixed shell micelles (MSMs) with approximately the same size, charge and core composition but with varied hydrophilic/hydrophobic ratios in the shell through spontaneously self-assembly of block copolymers poly(ethylene glycol)-block-poly(l-lysine) (PEG-b-PLys) and poly(N-isopropylacrylamide)-block-poly(aspartic acid) (PNIPAM-b-PAsp) in aqueous medium. The effect of the surface heterogeneity on the in vivo biodistribution was systematically investigated through in vivo tracking of the 125I-labeled MSMs determined by Gamma counter. Compared with single PEGylated micelles, some MSMs were proved to be significantly efficient with more than 3 times lower accumulation in liver and spleen and about 6 times higher concentration in blood at 1 h after i.v.. The results provide us a novel strategy for future development of long-circulating nanocarriers for efficient cancer therapy.
Co-reporter:Xue Liu, Hongjun Gao, Fan Huang, Xiaodong Pei, Yingli An, Zhenkun Zhang, Linqi Shi
Polymer 2013 Volume 54(Issue 14) pp:3633-3640
Publication Date(Web):21 June 2013
DOI:10.1016/j.polymer.2013.05.001
Multicompartment polymeric micelles (MPMs) have attracted broad interest, due to their intriguing advantages. Although a plethora of MPMs have been designed recently, characterization of the fine hierarchical compartmented structure and dynamic conformation change of MPMs are still challenging. In this contribution, we reported a strategy to detect thermo-induced structure rearrangement of one kind of MPMs--mixed shell polymeric micelles (MSPMs) and its interaction with bio-targets such as proteins by the means of the 1-anilino-8-naphthalene sulfonate (ANS) fluorescence. It is found that there exists a specific fluorescent emission phenomena characterized by a strong blue-shifted emission maximum and enhanced quantum yield when ANS interacts with MSPMs with a mixed shell consisting of homogeneously mixed poly(ethylene oxide) (PEG) and poly(N-isopropylacryamide) (PNIPAM). Such emission maximum was exploited to probe the structure evolution of MSPMs during the collapse of the thermo-sensitive PNIPAM component by heating. The variation of the emission behavior of ANS during heating is in line with the structure rearrangement of the MSPMs which critically depends on the nature of the micellar core. Binding of a model protein-carbonic anhydrase B (CAB) during heating induced denaturation to the hydrophobic PNIPAM domains of the MSPMs was also reflected by the change of the emission behavior of ANS.
Co-reporter:Lizhi Zhao, Ang Li, Rui Xiang, Liangliang Shen, and Linqi Shi
Langmuir 2013 Volume 29(Issue 28) pp:8936-8943
Publication Date(Web):2017-2-22
DOI:10.1021/la401805x
Aggregation of FeIII-tetra-(4-sulfonatophenyl)-porphyrin (FeIIITPPS) was studied in the presence of block copolymers, poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP), poly(ethylene glycol)-block-poly(2-(dimethylamino)ethyl methylacrylate) (PEG-b-PDMAEMA), and poly(ethylene glycol)-block-poly(β-cyclodextrin) (PEG-b-PCD). The interaction between the iron porphyrin and the blocks, P4VP, PDMAEMA, and PCD, led to the formation of copolymers/FeIIITPPS complex micelles with a PEG shell and determined the species of FeIIITPPS. The electrostatic interaction of protonated P4VP and PDMAEMA with FeIIITPPS remarkably decreased the apparent pKd of FeIIITPPS and led to a micellar μ-oxo dimer of the iron porphyrin. At pH above the pKa of P4VP, FeIIITPPS was kept inside the hydrophobic P4VP core and formed an encapsulated μ-oxo dimer. However, when above the pKa of PDMAEMA, FeIIITPPS escaped from the hydrophobic PDMAEMA core, existing as a free μ-oxo dimer. PCD caused the monomer of the porphyrin because of the inclusion complexation between the β-cyclodextrin residues and FeIIITPPS. The two micellar monomer species FeIIITPPS(H2O)2 and FeIIITPPS(OH) were obtained with an equilibrium pKa ∼ 6.4.
Co-reporter:Xue Liu;Yang Liu;Zhenkun Zhang;Fan Huang;Qian Tao;Rujiang Ma;Yingli An ; Linqi Shi
Chemistry - A European Journal 2013 Volume 19( Issue 23) pp:7437-7442
Publication Date(Web):
DOI:10.1002/chem.201300634
Abstract
We have fabricated a mixed-shell polymeric micelle (MSPM) that closely mimics the natural molecular chaperone GroELGroES complex in terms of structure and functionality. This MSPM, which possesses a shared PLA core and a homogeneously mixed PEG and PNIAPM shell, is constructed through the co-assembly of block copolymers poly(lactide-b-poly(ethylene oxide) (PLA-b-PEG) and poly(lactide)-b-poly(N-isopropylacryamide) (PLA-b-PNIPAM). Above the lower critical solution temperature (LCST) of PNIPAM, the MSPM evolves into a core–shell–corona micelle (CSCM), as a functional state with hydrophobic PNIPAM domains on its surface. Light scattering (LS), TEM, and fluorescence and circular dichroism (CD) spectroscopy were performed to investigate the working mechanism of the chaperone-like behavior of this system. Unfolded protein intermediates are captured by the hydrophobic PNIPAM domains of the CSCM, which prevent harmful protein aggregation. During cooling, PNIPAM reverts into its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The refolding process of the released proteins is spontaneously accomplished by the presence of PEG in the mixed shell. Carbonic anhydrase B (CAB) was chosen as a model to investigate the refolding efficiency of the released proteins. In the presence of MSPM, almost 93 % CAB activity was recovered during cooling after complete denaturation at 70 °C. Further results reveal that this MSPM also works with a wide spectrum of proteins with more-complicated structures, including some multimeric proteins. Given the convenience and generality in preventing the thermal aggregation of proteins, this MSPM-based chaperone might be useful for preventing the toxic aggregation of misfolded proteins in some diseases.
Co-reporter:Jie Ren, Yanxin Zhang, Ju Zhang, Hongjun Gao, Gan Liu, Rujiang Ma, Yingli An, Deling Kong, and Linqi Shi
Biomacromolecules 2013 Volume 14(Issue 10) pp:
Publication Date(Web):August 20, 2013
DOI:10.1021/bm4007387
Herein, a series of biocompatible, robust, pH/sugar-sensitive, core-cross-linked, polyion complex (PIC) micelles based on phenylboronic acid–catechol interaction were developed for protein intracellular delivery. The rationally designed poly(ethylene glycol)-b-poly(glutamic acid-co-glutamicamidophenylboronic acid) (PEG-b-P(Glu-co-GluPBA)) and poly(ethylene glycol)-b-poly(l-lysine-co-ε-3,4-dihydroxyphenylcarboxyl-l-lysine) (PEG-b-P(Lys-co-LysCA)) copolymers were successfully synthesized and self-assembled under neutral aqueous condition to form uniform micelles. These micelles possessed a distinct core-cross-linked core–shell structure comprised of the PEG outer shell and the PGlu/PLys polyion complex core bearing boronate ester cross-linking bonds. The cross-linked micelles displayed superior physiological stabilities compared with their non-cross-linked counterparts while swelling and disassembling in the presence of excess fructose or at endosomal pH. Notably, either negatively or positively charged proteins can be encapsulated into the micelles efficiently under mild conditions. The in vitro release studies showed that the release of protein cargoes under physiological conditions was minimized, while a burst release occurred in response to excess fructose or endosomal pH. The cytotoxicity of micelles was determined by cck-8 assay in HepG2 cells. The cytochrome C loaded micelles could efficiently delivery proteins into HepG2 cells and exhibited enhanced apoptosis ability. Hence, this type of core-cross-linked PIC micelles has opened a new avenue to intracellular protein delivery.
Co-reporter:Qian Tao, Ang Li, Xue Liu, Hongjun Gao, Zhenkun Zhang, Rujiang Ma, Yingli An, Linqi Shi
Colloids and Surfaces B: Biointerfaces 2013 Volume 111() pp:587-593
Publication Date(Web):1 November 2013
DOI:10.1016/j.colsurfb.2013.06.055
•Lipases and temperature-sensitive polymers are encapsulated in W/O microemulsion.•The thermal stability of lipase is effectively improved via this simple method.•The influences on the improvement and the mechanism of this method are discussed.•The stability of lipase at ambient temperature is also improved.•This method could be extended to other enzymes that are active in microemulsion.Lipase is active at the water–oil interface and thus very useful for many applications in non-aqueous media. However, the use of lipase is often limited due to the heat inactivation which is mainly caused by the irreversible aggregation among lipase molecules. The temperature-sensitive polymers can spontaneously form complexes with lipases at higher temperature in the confined spaces of the water in oil microemulsion. With cooling, lipases are released from the complexes and refold into the native state. In this way, the thermal stability of lipase in a microemulsion is effectively improved, and so is the stability of lipase at ambient temperature. Apart from proving the effectiveness and generality of this method, the temperature-sensitive polymers/lipase microemulsion represents a simple and efficient system which could be used in practical applications, since lipase retains the interfacial activity in this system. Moreover, the influences of some factors on the improvement are discussed and the mechanism of this method is suggested after exploring the process by dynamic light scattering and fluorescence measurements.
Co-reporter:Yaohua Gao;Cuihong Yang;Xue Liu;Rujiang Ma;Deling Kong
Macromolecular Bioscience 2012 Volume 12( Issue 2) pp:251-259
Publication Date(Web):
DOI:10.1002/mabi.201100208
Co-reporter:Xiaojun Liu, Rujiang Ma, Junyang Shen, Yanshuang Xu, Yingli An, and Linqi Shi
Biomacromolecules 2012 Volume 13(Issue 5) pp:
Publication Date(Web):March 19, 2012
DOI:10.1021/bm2018382
Oral administration of ionic drugs generally encounters with significant fluctuation in plasma concentration due to the large variation of pH value in the gastrointestinal tract and the pH-dependent solubility of ionic drugs. Polymeric complex micelles with charged channels on the surface provided us with an effective way to reduce the difference in the drug release rate upon change in pH value. The complex micelles were prepared by self-assembly of PCL-b-PAsp and PCL-b-PNIPAM in water at room temperature with PCL as the core and PAsp/PNIPAM as the mixed shell. With an increase in temperature, PNIPAM collapsed and enclosed the PCL core, while PAsp penetrated through the PNIPAM shell, leading to the formation of negatively charged PAsp channels on the micelle surface. Release behavior of ionic drugs from the complex micelles was remarkably different from that of usual core–shell micelles where diffusion and solubility of drugs played a key role. Specifically, it was mainly dependent on the conformation of the PAsp chains and the electrostatic interaction between PAsp and drugs, which could partially counteract the influence of pH-dependent diffusion and solubility of drugs. As a result, the variation of drug release rate with pH value was suppressed, which was favorable for acquiring relatively steady plasma drug concentration.
Co-reporter:Rujiang Ma, Hao Yang, Zhong Li, Gan Liu, Xiaocheng Sun, Xiaojun Liu, Yingli An, and Linqi Shi
Biomacromolecules 2012 Volume 13(Issue 10) pp:
Publication Date(Web):September 7, 2012
DOI:10.1021/bm3012715
Polymeric nanoparticles with glucose-responsiveness under physiological conditions are of great interests in developing drug delivery system for the treatment of diabetes. Herein, glucose-responsive complex micelles were prepared by self-assembly of a phenylboronic acid-contained block copolymer PEG-b-P(AA-co-APBA) and a glycopolymer P(AA-co-AGA) based on the covalent complexation between phenylboronic acid and glycosyl. The formation of the complex micelles with a P(AA-co-APBA)/P(AA-co-AGA) core and a PEG shell was confirmed by HNMR analysis. The glucose-responsiveness of the complex micelles was investigated by monitoring the light scattering intensity and the fluorescence (ARS) of the micelle solutions. The complex micelles displayed an enhanced glucose-responsiveness compared to the simple PEG-b-P(AA-co-APBA) micelles and the sensitivity of the complex micelles to glucose increased with the decrease of the amount of P(AA-co-AGA) in the compositions. The cytotoxicity of the polymers and the complex micelles was also evaluated by MTT assay. This kind of complex micelles may be an excellent candidate for insulin delivery and may find application in the treatment of diabetes.
Co-reporter:Yanling Xu, Rujiang Ma, Zhenkun Zhang, Huan He, Yaozong Wang, Aoting Qu, Yingli An, X.X. Zhu, Linqi Shi
Polymer 2012 Volume 53(Issue 16) pp:3559-3565
Publication Date(Web):19 July 2012
DOI:10.1016/j.polymer.2012.05.064
Complex polymeric micelles with a PLA core and a mixed PEG/PNIPAM shell were prepared by self-assembly of two block copolymers: poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) and poly(N-isopropylacrylamide)-b-poly(lactic acid) (PNIPAM-b-PLA). Using 1H NMR spectroscopy and dynamic light scattering, the micellization and the enzymatic degradation status were characterized. At 25 °C, the PNIPAM block is hydrophilic and the PLA core is prone to the enzymatic degradation, resulting in the disassembly of the micelles. While increasing the temperature to 45 °C, the PNIPAM collapsed onto the PLA core, protecting the PLA core from the attack by the enzyme, and the micelles exhibit a resistance to the enzymatic degradation. Furthermore, the enzymatic degradation rate of the micelles can also be tuned by changing the ratio of PEG to PNIPAM. With increasing content of PNIPAM, the conformation of the collapsed PNIPAM changes from patchy domains to a continuous and dense layer, and the enzyme accessibility to the PLA core is changed.
Co-reporter:Yaohua Gao, Rujiang Ma, De’an Xiong, Xin Wang, Yingli An, Linqi Shi
Carbohydrate Polymers 2011 Volume 83(Issue 4) pp:1611-1616
Publication Date(Web):1 February 2011
DOI:10.1016/j.carbpol.2010.10.012
Monodisperse hollow spheres with radially oriented α-cyclodextrin nanotube assembled shells were synthesized using PEG-grafted silica as templates. (3-Aminopropyl)triethoxysilane-modified silica core was synthesized by the Stöber method and subsequently grafted with mPEG-succinimidyl carbonate through amide linkage. Maleic anhydride modified α-cyclodextrins were threaded onto the grafted-PEG chains, forming tubular polypseudorotaxanes. Adjacent polypseudorotaxanes were immobilized by crosslinking. After the extraction of the inner silica template by etching and the included PEG template by heating, hollow spheres of uniform size with α-CD nanotube assembled shells were prepared. The products were composed of intact and dispersed hollow spheres with diameter of about 50 nm, possessed uniform shell thickness of 12 nm as confirmed by transmission electron microscopy (TEM) measurement. α-CD nanotubes have a function of molecular recognization with PEG, which may endow the hollow nanospheres as promising target drug delivery vehicles by forming inclusion complexes with end-functionalized PEG.
Co-reporter:Qian Tao, Ang Li, Xue Liu, Rujiang Ma, Yingli An and Linqi Shi
Physical Chemistry Chemical Physics 2011 vol. 13(Issue 36) pp:16265-16271
Publication Date(Web):15 Aug 2011
DOI:10.1039/C1CP21438A
At high temperature, many enzymes are inactivated by aggregations at hydrophobic sites which are exposed on denaturation. Isolating denatured enzymes via hydrophobic interactions with other material is a significant method to prevent enzymes from aggregation. But the temperature-sensitive polymer poly(N-isopropylacrylamide) (PNIPAAm), supposed to protect enzymes spontaneously at high temperatures, can not efficiently complex denatured carbonic anhydrase B (CAB, as a model enzyme) in bulk aqueous solution due to different phase transition speeds. Here, we present a novel method for protecting enzymes against heat inactivation, in which PNIPAAm and CAB are encapsulated in a confined space constructed by reverse microemulsion. At high temperatures, PNIPAAm forms nanoscale aggregates possessing both large specific surface areas and hydrophobic surfaces, and then adsorbs denatured CABvia hydrophobic interactions to avoid intermolecular aggregation of CAB. With cooling, CAB is released spontaneously and recovers its activity. The assays for enzymatic activity demonstrate that CAB is effectively protected against heat inactivation through this method (protection efficiency is up to 83.2%).
Co-reporter:Yang Liu;Dr. Hao Wang;Dr. Ken-ichiro Kamei;Dr. Ming Yan;Kuan-Ju Chen;Qinghua Yuan; Linqi Shi; Yunfeng Lu; Hsian-Rong Tseng
Angewandte Chemie International Edition 2011 Volume 50( Issue 13) pp:3058-3062
Publication Date(Web):
DOI:10.1002/anie.201005740
Co-reporter:Zhaoye Li;Rujiang Ma;Ang Li;Huan He;Yingli An
Colloid and Polymer Science 2011 Volume 289( Issue 13) pp:1429-1435
Publication Date(Web):2011 August
DOI:10.1007/s00396-011-2434-8
In this paper, multicolored micelles were prepared by coordination of lanthanide(III) (europium(III) (Eu(III)) and terbium(III) (Tb(III))) ions with block copolymer in different molar ratios of nEu(III)/nTb(III). The micelles formed by polymer–Eu(III)/Tb(III) could emit higher quantum yield luminescence than the mixture of polymer–Eu(III) micelles and polymer–Tb(III) micelles. The micelles containing Eu(III) and Tb(III) could emit a yellow-green color, and the intensity varied with the molar ratios of nEu(III)/nTb(III). In the constant concentrations of Eu(III) and 1,10-phenanthroline (Phen), the intensity of 5D0→7F2 increased with the addition of Tb(III), and the intensity of 5D4→7F5 decreased with the increasing of Eu(III) in the constant concentrations of Tb(III) and Phen. All the multicolored micelles could be spin-coated as intensity-tunable films.
Co-reporter:LiZhi Zhao;Rui Xiang;LiYan Zhang;ChengLin Wu;RuJiang Ma
Science China Chemistry 2011 Volume 54( Issue 2) pp:343-350
Publication Date(Web):2011 February
DOI:10.1007/s11426-010-4202-x
Aggregation of 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin (TPPS) was investigated in complex micelles composed of poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP) and poly(2-(dimethylamino)ethyl methylacrylate)-b-poly(N-isopropylacrylamide) (PDMAEMA-b-PNIPAM) in aqueous solutions. The resultant complex micelles had a complex P4VP/PDMAEMA/TPPS core and a mixed PEG/PNIPAM shell. Different noncovalent interaction modes between the porphyrin and each copolymer accomplished a co-effect on the aggregation of TPPS. The formation of aggregates was pH-dependent. At pH 3.2–6.5, TPPS existed as a mixture of H-aggregates and monomers because of the aromatic-aromatic interaction with P4VP and electrostatic interaction with PDMAEMA. The monomers translated into J-aggregates, stabilized by electrostatic interaction with the both polyelectrolyte blocks, upon decreasing the pH to 1.6. The free-base monomer was the one and only form for the dye at pH 11.0 due to aromatic stacking with the pyridyl rings.
Co-reporter:Lizhi Zhao, Rui Xiang, Rujiang Ma, Xin Wang, Yingli An, and Linqi Shi
Langmuir 2011 Volume 27(Issue 18) pp:11554-11559
Publication Date(Web):August 16, 2011
DOI:10.1021/la201434r
In the presence of tryptophan (Trp), complex micelles were prepared by 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (TPPS) and poly(ethylene glycol)-block-poly(2-(dimethylamino)ethyl methylacrylate) (PEG-b-PDMAEMA) in aqueous solutions at pH 1.8. Different mixing sequences led to different morphologies. Spheres and nanorods of small size were obtained in sequence I (P/Trp+TPPS) where TPPS was added into the mixed solution of PEG-b-PDMAEMA and Trp. More nanorods of larger length were achieved in sequence II (TPPS/Trp+P) where the copolymer was added as the last component. Two types of supramolecular chirality of TPPS aggregates caused by mixing sequences were investigated. In (P/Trp+TPPS), the circular dichroism (CD) signal of H-band was in line with the chirality of Trp while that of J-band exhibited an opposite signal (Chirality I). In (TPPS/Trp+P), chiral signals at both H- and J-bands followed that of Trp (Chirality II). The conversion between the two types of chirality can be accomplished by modulating the molar ratio of the repeating units on block PDMAEMA to TPPS, or a cycle of pH 1.8–5.5–1.8 processing on the micelle solution. In addition, the supramolecular chirality can be memorized via strong electrostatic interaction with achiral copolymer even after removal of the chiral template, but only Chirality II can be cyclically “switched-off-on”.
Co-reporter:Xin Wang, Lizhi Zhao, Rujiang Ma, Yingli An and Linqi Shi
Chemical Communications 2010 vol. 46(Issue 35) pp:6560-6562
Publication Date(Web):16 Aug 2010
DOI:10.1039/C0CC01674H
Poly(ethyleneglycol)-b-poly(4-vinylpyridine) (PEG-b-P4VP) and zinc meso-5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin (ZnTPPS) form complex micelles based on electrostatic interactions. The complex micelles have a core-shell structure that can effectively prevent the demetallization and aggregation of ZnTPPS in acidic aqueous solutions (pH < 4.0).
Co-reporter:Beilei Wang;Rujiang Ma;Gan Liu;Xiaojun Liu;Yaohua Gao;Junyang Shen;Yingli An
Macromolecular Rapid Communications 2010 Volume 31( Issue 18) pp:1628-1634
Publication Date(Web):
DOI:10.1002/marc.201000164
Co-reporter:Yan Li, Qian Tao, Lizhi Zhao, Rujiang Ma, Yingli An and Linqi Shi
Physical Chemistry Chemical Physics 2010 vol. 12(Issue 37) pp:11380-11389
Publication Date(Web):16 Aug 2010
DOI:10.1039/B927056F
To explore the structure and property features of complex aggregates assembled by polymer and organic dye molecules in microcosmic soft confined space, a three-dimensional microconfinement is constructed by W/O inverse emulsion as the site for the complex aggregation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP). It is found that porphyrin molecules exist in emulsion droplets mainly as the deprotonated monomer form, even though the pH of the water phase is much lower than the pKa of TPPS in bulk (pKa ≈ 4.7). In spatially confined circumstances, upon blending of the single-component emulsions, complex aggregates are formed due to the thermodynamic collision of emulsion droplets and the subsequent electrostatic interaction between TPPS and polymer. The resultant novel complexes possess a relatively precise structure and homogenous core consisting of a porphyrin and P4VP block. Upon emulsion-breaking, the metastable complex kinetic intermediates generated in original acidic emulsion droplets display a remarkable trend of reaggregation within a certain period of time followed by a disassociation and redispersion. Complex aggregates with some novel morphologies are observed. The final product has a core–shell structure with the electrostatic complex of deprotonized porphyrin molecules homogenously dispersing in the P4VP clew as the core and the soluble PEG as the shell. However, those complexes produced in basic emulsion droplets exhibit a relatively higher stability against further aggregation after breakage of emulsion.
Co-reporter:Rujiang Ma
Macromolecular Bioscience 2010 Volume 10( Issue 12) pp:1397-1405
Publication Date(Web):
DOI:10.1002/mabi.201000171
Co-reporter:De’an Xiong, Zhe Li, Lu Zou, Zhenping He, Yang Liu, Yingli An, Rujiang Ma, Linqi Shi
Journal of Colloid and Interface Science 2010 Volume 341(Issue 2) pp:273-279
Publication Date(Web):15 January 2010
DOI:10.1016/j.jcis.2009.09.045
Polymeric micelles with a polystyrene core, poly(acrylic acid)/poly(4-vinyl pyridine) (PAA/P4VP) complex shell and poly(ethylene glycol) & poly(N-isopropylacrylamide) (PEG & PNIPAM) mixed corona were synthesized and used as the supporter for the gold nanoparticles (GNs). It was concluded from the result of 1H NMR characterization that hydrophilic channels formed around PEG chains when PNIPAM collapsed above its lower critical solution temperature. The density of the channels in the corona can be tuned by changing the weight ratios of PEG chains to PNIPAM chains. The GNs were set in the PAA/P4VP complex layer and the catalytic activity of the GNs can be modulated by the channels. The catalytic activity increased with increasing the density of the channels in the corona. Meanwhile, the whole Au/micelle nanoparticles were stabilized by the extended PEG chains.Hydrophilic channels were constructed in the corona of the polymeric micelles and used to tune the catalytic activity of the supported gold nanoparticles.
Co-reporter:ChengLin Wu;Huan He;HongJun Gao;Gan Liu;RuJiang Ma
Science China Chemistry 2010 Volume 53( Issue 3) pp:514-518
Publication Date(Web):2010 March
DOI:10.1007/s11426-010-0084-1
Novel multifunctional nanoparticles containing a magnetic Fe3O4@SiO2 sphere and a biocompatible block copolymer poly(ethylene glycol)-b-poly(aspartate) (PEG-b-PAsp) were prepared. The silica coated on the superparamagnetic core was able to achieve a magnetic dispersivity, as well as to protect Fe3O4 against oxidation and acid corrosion. The PAsp block was grafted to the surface of Fe3O4@SiO2 nanoparticles by amido bonds, and the PEG block formed the outermost shell. The anticancer agent doxorubicin (DOX) was loaded into the hybrid nanoparticles via an electrostatic interaction between DOX and PAsp. The release rate of DOX could be adjusted by the pH value.
Co-reporter:Chenglin Wu, Xin Wang, Lizhi Zhao, Yaohua Gao, Rujiang Ma, Yingli An, and Linqi Shi
Langmuir 2010 Volume 26(Issue 23) pp:18503-18507
Publication Date(Web):November 9, 2010
DOI:10.1021/la103629v
The silica/polymer hybrid hollow nanoparticles with channels and gatekeepers were successfully fabricated with a facile strategy by using thermoresponsive complex micelles of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(N-isopropylacrylamide)-b-poly(4-vinylpyridine) (PNIPAM-b-P4VP) as the template. In aqueous solution, the complex micelles (PEG-b-PNIPAM/PNIPAM-b-P4VP) formed with the PNIPAM block as the core and the PEG/P4VP blocks as the mixed shell at 45 °C and pH 4.0. After shell cross-linking by 1,2-bis(2-iodoethoxyl)ethane (BIEE), tetraethylorthosilicate (TEOS) selectively well-deposited on the P4VP block and processed the sol−gel reaction. When the temperature was decreased to 4 °C, the PNIPAM block became swollen and further soluble, and the PEG-b-PNIPAM block copolymer escaped from the hybrid nanoparticles as a result of swelled PNIPAM and weak interaction between PEG and silica at pH 4.0. Therefore, the hybrid hollow silica nanoparticles with inner thermoresponsive PNIPAM as gatekeepers and channels in the silica shell were successfully obtained, which could be used for switchable controlled drug release. In the system, the complex micelles, as a template, could avoid the formation of larger aggregates during the preparation of the hybrid hollow silica nanoparticles. The thermoresponsive core (PNIPAM) could conveniently control the hollow space through the stimuli-responsive phase transition instead of calcination or chemical etching. In the meantime, the channel in the hybrid silica shell could be achieved because of the escape of PEG chains from the hybrid nanoparticles.
Co-reporter:Zhaoye Li;Rujiang Ma;Yingli An
Colloid and Polymer Science 2010 Volume 288( Issue 9) pp:1041-1046
Publication Date(Web):2010 June
DOI:10.1007/s00396-010-2237-3
Luminescent micelles were prepared through the self-assembly of poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG114-b-P4VP61) and Europium(III) (Eu(III)), with P4VP/Eu(III) as the core, and PEG as the corona. 1,10-phenanthroline (Phen) was assembled into the core of the micelles to sensitize the luminescence. The presence of Phen results into the increasing of apparent average hydrodynamic diameters (\( {\hbox{D}}_{\rm{h}}^{\rm{app}} \)) of the micelles. All Eu(III)-containing micelles emitted the characteristic fluorescence of Eu(III). The intensity of luminescence increased with the presence and the increasing quantity of Phen in the complex micelles due to the effective energy transferring of Phen in the “antenna effect”.
Co-reporter:Dongyun Zhao, Xi Chen, Yang Liu, Chenglin Wu, Rujiang Ma, Yingli An, Linqi Shi
Journal of Colloid and Interface Science 2009 Volume 331(Issue 1) pp:104-112
Publication Date(Web):1 March 2009
DOI:10.1016/j.jcis.2008.11.041
The bimetallic nanoparticles were protected by a double stimuli-sensitive diblock copolymer, poly(N-isopropylacrylamide)-block-poly(4-vinylpyridine) (PNIPAM-b-P4VP), which was synthesized via the reversible addition–fragmentation chain transfer (RAFT) polymerization. The obtained nanocomposites were made up of bimetallic nanoparticles cross-linked P4VP core and PNIPAM shell. Energy-dispersive X-ray (EDX) spectra and UV–vis transmittance revealed the formed nanoparticles was truly bimetallic particles with incomplete core–shell structures, Au as core and Pd as shell, rather than the physical mixture of monometallic nanoparticles. Laser light scattering (LLS) demonstrated the nanocomposites exhibit both thermo and pH sensitivity. X-ray diffraction (XRD) clearly showed Au formed a high-ordered crystal while Pd fashioned amorphous aggregates. In addition, the bimetallic nanocomposites show special responsiveness for temperature and better catalytic activity than corresponding monometallic nanocomposites.The bimetallic nanocomposites made up of bimetallic nanoparticles cross-linked P4VP core and PNIPAM shell show well thermo and pH sensitivity.
Co-reporter:Chenglin Wu;Rujiang Ma;Huan He;Lizhi Zhao;Hongjun Gao;Yingli An
Macromolecular Bioscience 2009 Volume 9( Issue 12) pp:1185-1193
Publication Date(Web):
DOI:10.1002/mabi.200900232
Co-reporter:De'an Xiong;Zhe Li;Rujiang Ma;Yingli An
Journal of Polymer Science Part A: Polymer Chemistry 2009 Volume 47( Issue 6) pp:1651-1660
Publication Date(Web):
DOI:10.1002/pola.23268
Abstract
Hollow crosslinked polymers (HCPs) were synthesized using arm first method via atom transfer radical polymerization. The polymerization process was performed in miniemulsion system, in which the macroinitiator, PEG-Br, was in the water phase, whereas the vinyl-monomer, 4-vinylpyridine (4VP), and the crosslinker, DVB, were in the butanone phase. TEM images and light scattering characterization showed that the resultant polymer contained a hollow space, and the volume of the hollow space could be adjusted by changing the ratio of water to butanone. Also, hollow crosslinked Miktoarm polymers (HCMPs) were synthesized through this method when two different macroinitiators, PEG-Br and PNIPAM-Br, were used to coinitiate the polymerization of the vinyl-monomer, 4VP and DVB. The 1H NMR spectra showed that the hollow polymers contained both PEG arms and PNIPAM arms. The hollow morphologies of the resultant Miktoarm polymers were the same as the HCPs. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1651–1660, 2009
Co-reporter:Lizhi Zhao, Xin Wang, Yan Li, Rujiang Ma, Yingli An and Linqi Shi
Macromolecules 2009 Volume 42(Issue 16) pp:6253-6260
Publication Date(Web):July 27, 2009
DOI:10.1021/ma900925q
Chiral complex micelles prepared by 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and the poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG114-b-P4VP61) in the presence of aspartic acid (Asp), tryptophan (Trp), and lysine (Lys) were investigated in aqueous solutions at pH 2.0. TPPS formed J-aggregates in the micellar core. The morphology and optical properties of the complex micelles depended on the properties of amino acids and the preservation time for the mixed solutions of TPPS and amino acids before adding the copolymer. Prolonging the preservation time, the spherical morphology of the complex micelles remained unchanged in the presence of the Asp. On the contrary, a morphology evolution from sphere to rod took place for Trp and Lys. The intensity of the circular dichroism (CD) signals of the complex micelles increase with the preservation time, and the chirality sign was determined by amino acids. l-Trp and l-Lys led to a negative chirality sign and l-Asp a positive one while the corresponding enantiomers contributed to the opposite sign. Lower concentration of amino acids could not transfer their chirality to the aggregates of TPPS, and at higher concentrations of TPPS, it took more time for the aggregates to express the chiral information on amino acids.
Co-reporter:Xi Chen;DongYun Zhao;LiZhi Zhao;YingLi An
Science China Chemistry 2009 Volume 52( Issue 9) pp:1372-1381
Publication Date(Web):2009 September
DOI:10.1007/s11426-009-0154-4
Gold nanoparticles (GNs) are prepared through in situ reduction using NaBH4 in the presence of homopolymer PDMAEMA. The sizes of the GNs can be adjusted by alternating the molar ratio of gold to DMAEMA. Pure PDMAEMA aqueous solution shows a phase-transition at 50°C at pH 10 and 25°C at pH 14, while PDMAEMA-supported GNs aqueous solution shows a phase-transition at 47°C at pH 10 because of the increasing hydrophobic property resulting from GNs. Due to the pH and temperature-responsible characteristics of PDMAEMA, the resulting PDMAEMA-supported GNs exhibit pH adjustable temperature-responsive characteristics in optic and catalytic aspects. Under an acidic condition (pH 2), the GNs show unchanged surface Plasmon absorbance with a peak of 518 nm in a temperature range from 20 to 65°C. Under a basic condition (pH 10), the GNs first show the same absorbance with a peak at 518 nm in a temperature range from 20 to 40°C, and then the absorbance red shifts from 518 to 545 nm as temperature increases from 40 to 65°C. When the GNs are used as catalysts to catalyze the reduction of p-nitrophenol, the catalytic activity can be adjusted by changing the permeation of reactants in the PDMAEMA layer at low and high temperatures, respectively.
Co-reporter:Yang Liu, Dongyun Zhao, Rujiang Ma, De'an Xiong, Yingli An, Linqi Shi
Polymer 2009 50(3) pp: 855-859
Publication Date(Web):
DOI:10.1016/j.polymer.2008.12.005
Co-reporter:Zhe Li, De'an Xiong, Bing Xu, Chenglin Wu, Yingli An, Rujiang Ma, Linqi Shi
Polymer 2009 50(3) pp: 825-831
Publication Date(Web):
DOI:10.1016/j.polymer.2008.12.004
Co-reporter:Yan Li, Rujiang Ma, Lizhi Zhao, Qian Tao, De’an Xiong, Yingli An and Linqi Shi
Langmuir 2009 Volume 25(Issue 5) pp:2757-2764
Publication Date(Web):February 9, 2009
DOI:10.1021/la803996b
To mimic nanostructures assembled by biomolecules in organic cells and achieve precise self-assembly of block copolymers, a simple but valid way is introduced to quasi-quantificationally control the aggregation numbers (Nagg) of polymeric micelles. A three-dimensional and closed microconfinement similar to a cell is constructed by W/O inverse emulsion as the spot for self-assembly of the pH-responsive block copolymer poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP). The Nagg values of the resulting polymeric micelles are effectively controlled by tuning the number of polymer chains encapsulated in isolated water pools. Micelles with different Nagg values are successfully prepared and characterized by atomic force microscopy, transmission electron microscopy, and dynamic light scattering. When the number of polymer chains enclosed in a water pool (Nchain) is less than the average Nagg of normal micelles generated in bulk aqueous solution, the resultant aggregates formed in the confined spaces always have lower Nagg as well as smaller sizes than the normal micelles do, while normal micelles predominantly form when Nchain > Nagg (normal micelle).
Co-reporter:Lizhi Zhao, Rujiang Ma, Junbo Li, Yan Li, Yingli An and Linqi Shi
Biomacromolecules 2009 Volume 10(Issue 12) pp:
Publication Date(Web):November 6, 2009
DOI:10.1021/bm9010408
Co-reporter:Junbo Li;Yingli An;Xi Chen;De'an Xiong;Yan Li;Nan Huang
Macromolecular Rapid Communications 2008 Volume 29( Issue 3) pp:214-218
Publication Date(Web):
DOI:10.1002/marc.200700567
Co-reporter:Huan Wang;Yingli An;Nan Huang;Rujiang Ma;Junbo Li
Macromolecular Rapid Communications 2008 Volume 29( Issue 16) pp:1410-1414
Publication Date(Web):
DOI:10.1002/marc.200800137
Co-reporter:De'an Xiong;Yingli An;Zhe Li;Rujiang Ma;Yang Liu;Chenglin Wu;Lu Zou;Junhua Zhang
Macromolecular Rapid Communications 2008 Volume 29( Issue 23) pp:1895-1901
Publication Date(Web):
DOI:10.1002/marc.200800300
Co-reporter:Xi Chen, Dongyun Zhao, Yingli An, Yan Zhang, Jing Cheng, Beilei Wang, Linqi Shi
Journal of Colloid and Interface Science 2008 Volume 322(Issue 2) pp:414-420
Publication Date(Web):15 June 2008
DOI:10.1016/j.jcis.2008.03.029
Micelle-supported gold composites with a polystyrene core and a poly(4-vinyl pyridine)/Au shell are synthesized using NaBH4 to reduce a mixture of micelle and HAuCl4 in acidic aqueous solution (pH ∼2). The template micelle with a polystyrene core and a poly(4-vinyl pyridine) shell is formed by self-assembly of block copolymer polystyrene-block-poly(4-vinyl pyridine). The gold nanoparticles coated onto the surfaces of the composites possess an average diameter of about 15 nm. The composites are applied to catalyze the reduction of p-nitrophenol in the presence of NaBH4, and the results indicate that the kinetic constant of the reaction increases when the composite concentration and the reaction temperature increase. In addition, research results also indicate that composites with high content of gold show higher catalytic activity and higher catalytic efficiency.The metal ions (AuCl−4) are confined within the shell of the core–shell micelles. Reduction of the metal ions leads to the nanosized gold particles on the core surface.
Co-reporter:Lizhi Zhao, Rujiang Ma, Junbo Li, Yan Li, Yingli An and Linqi Shi
Biomacromolecules 2008 Volume 9(Issue 10) pp:
Publication Date(Web):August 14, 2008
DOI:10.1021/bm8004808
Micellization of poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG114-b-P4VP61) induced by 5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrin (TPPS) in acidic solutions were studied by dynamic and static light scattering, atomic force microscope, and UV−vis spectroscopy. The resultant complex micelles had a core−shell structure with the electrostatically complex TPPS/P4VP as the core and the soluble PEG as the shell. The anionic TPPS in the micellar core formed J-aggregates at pH 1.5−2.5 and H-aggregates at pH 3.0−4.0, respectively. Interconversion between the J-aggregates and the H-aggregates was carried out by adjusting the pH value of the micelle solutions. It is worth noting that the micelles showed strong split Cotton effect in the circular dichroism spectra although TPPS and the copolymer were all achiral. The resulting chirality sign could be selected by the hydrodynamic forces of a stirring vortex. Positive or negative chiral signals appeared when stirring clockwise or anticlockwise.
Co-reporter:Xi Chen, Yingli An, Dongyun Zhao, Zhenping He, Yan Zhang, Jing Cheng and Linqi Shi
Langmuir 2008 Volume 24(Issue 15) pp:8198-8204
Publication Date(Web):June 25, 2008
DOI:10.1021/la800244g
Micelles having a core of polystyrene and a mixed shell of poly(ethylene glycol) and poly(4-vinylpyridine) were formed through self-assembly of a triblock copolymer poly(ethylene glycol)-block-polystyrene-block-poly(4-vinylpyridine) in acidic water (pH 2). Reducing the HAuCl4-treated micelle solution leads to the formation of the Au−micelle composites with a core of polystyrene, a hybrid shell of poly(4-vinylpyridine)/Au/poly(ethylene glycol), and a corona of poly(ethylene glycol). The gold nanoparticles with controlled sizes were anchored to poly(4-vinylpyridine) to form the physically cross-linked hybrid shell. In aqueous solution, the hybrid shell is swollen and the swollen degree is sensitive to the pH condition. Under basic conditions, the channel in the hybrid shells of the composite is produced, which renders the composites a good catalytic activity. In addition, the composites also show good stability, unchanged hydrodynamic diameter, and surface plasmon absorption under different pH conditions.
Co-reporter:Linqi Shi;Xiaowei Jiang;Yingli An;Xi Chen;Juan Lü;De'an Xiong
Macromolecular Rapid Communications 2007 Volume 28(Issue 2) pp:194-199
Publication Date(Web):22 JAN 2007
DOI:10.1002/marc.200600681
Worm-like aggregates with a PAA/P4VP complex core and a PEG/PNIPAM mixed shell were prepared in ethanol by the comicellization of poly(ethylene glycol)-block-poly(acrylic acid) (PEG-b-PAA) and poly(N-isopropylacrylamide)-block-poly(4-vinylpyridine) (PNIPAM-b-P4VP) through hydrogen-bonding. The formed aggregates were studied by dynamic light scattering, static light scattering, 1H NMR, and transmission electron microscopy. The length of worm-like aggregates could be adjusted by changing the weight ratio of W(PNIPAM-b-P4VP)/W(PEG-b-PAA). When the ratio changed from 20 to 150%, the length changed from about 100 nm to several microns, and the diameter stayed almost unchanged at about 15 nm.
Co-reporter:Xi Chen;Yang Liu;Juan Lü;Yingli An;Junbo Li;Dean Xiong
Macromolecular Rapid Communications 2007 Volume 28(Issue 12) pp:1350-1355
Publication Date(Web):12 JUN 2007
DOI:10.1002/marc.200700166
We report a simple procedure to prepare a novel Au-micelle composite with a core-shell-corona structure. This composite is prepared by reduction of tetrachloroauric acid (HAuCl4 · 3H2O) in dilute aqueous solution containing polystyrene-block-poly(4-vinylpyridine) micelles and poly(ethylene oxide)-block-poly(4-vinylpyridine) copolymers. The micelles with a polystyrene core and a poly(4-vinylpyridine) shell are transformed into Au-micelle composites with a polystyrene core, a swollen hybrid Au/poly(4-vinylpyridine) inner shell, and a poly(ethylene oxide) corona by direct physisorption of gold particles with poly(4-vinylpyridine) chains.
Co-reporter:Beilei Wang;Rujiang Ma;Yingli An;Yanling Xu;Wangqing Zhang;Guiying Li
Macromolecular Rapid Communications 2007 Volume 28(Issue 9) pp:1062-1069
Publication Date(Web):24 APR 2007
DOI:10.1002/marc.200600843
Complex micelles with a P4VP core surrounded by a mixed PNIPAM/PEG shell were prepared by comicellization of PNIPAM93-b-P4VP58 and PEG114-b-P4VP58 in aqueous solutions. Increasing the temperature above the LCST of the PNIPAM induced a phase separation of the mixed shell due to the collapse of the PNIPAM block. The morphology of the collapsed PNIPAM was dependent on the composition of the mixed shell; a lower content of the PNIPAM resulted in separately distributed domains on the surface of the P4VP core, while a higher content of the PNIPAM led to the formation of continuous membrane around the P4VP core. When the continuous membrane was formed, the hydrophilic PEG block could connect the inner P4VP core and the outer milieu to form channels across the PNIPAM membrane for water and other small molecules to pass through.
Co-reporter:Yingli An;Xiaowei Jiang;Wangqing Zhang;De'An Xiong;Peiwen Zheng
Journal of Polymer Science Part A: Polymer Chemistry 2007 Volume 45(Issue 13) pp:2812-2819
Publication Date(Web):18 MAY 2007
DOI:10.1002/pola.22037
The synthesis of a thermoresponsive hydrogel of poly(glycidyl methacrylate-co-N-isopropylacrylamide) (PGMA-co-PNIPAM) and its application as a nanoreactor of gold nanoparticles are studied. The thermoresponsive copolymer of PGMA-co-PNIPAM is first synthesized by the copolymerization of glycidyl methacrylate and N-isopropylacrylamide using 2,2′-azobis(isobutyronitrile) as an initiator in tetrahydrofuran at 70 °C and then crosslinked with diethylenetriamine to form a thermoresponsive hydrogel. The lower critical solution temperature (LCST) of the thermoresponsive hydrogel is about 50 °C. The hydrogel exists as 280-nm spheres below the LCST. The diameter of the spherical hydrogel gradually decreases to a minimum constant of 113 nm when the temperature increases to 75 °C. The hydrogel can act as a nanoreactor of gold nanoparticles because of the coordination of nitrogen atoms of the crosslinker with gold ions, on which a hydrogel/gold nanocomposite is synthesized. The LCST of the resultant hydrogel/gold nanocomposite is similar to that of the hydrogel. The size of the resultant gold nanoparticles is about 15 nm. The hydrogel/gold nanocomposite can act as a smart and recyclable catalyst. At a temperature below the LCST, the thermoresponsive nanocomposite is a homogeneous and efficient catalyst, whereas at a temperature above the LCST, it becomes a heterogeneous one, and its catalytic activity greatly decreases. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2812–2819, 2007
Co-reporter:Xiaowei Jiang;Yao Wang;Peiwen Zheng;Wangqing Zhang
Macromolecular Rapid Communications 2006 Volume 27(Issue 21) pp:1833-1837
Publication Date(Web):2 NOV 2006
DOI:10.1002/marc.200600481
Summary: Raspberry-like aggregates containing secondary nanospheres were studied. The formation of raspberry-like aggregates was due to complexation between core-shell microspheres and core-corona micelles. The core-shell microspheres were synthesized with soap-free polymerization of styrene and methyl acrylic acid, which included carboxyl groups in the periphery. The micelles were self-assembled by polystyrene-block-poly(4-vinylpyridine), which contained pyridine groups in the corona. The driven force to form raspberry-like aggregates was due to the affinity between the carboxyl and pyridine groups. The morphology of the raspberry-like aggregates could be tuned by changing the ratio of the microspheres to micelles. IR measurements suggested that the raspberry-like aggregates were like zwitterions.
Co-reporter:Kai Wu;Wangqing Zhang;Xiao-Xia Zhu;Yingli An
Journal of Applied Polymer Science 2006 Volume 102(Issue 4) pp:3144-3148
Publication Date(Web):29 AUG 2006
DOI:10.1002/app.24300
This article presents a new and promising way to design a temperature sensor, which is based on the micellization or aggregation behavior of binary diblock copolymers of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) and poly(ethylene glycol)-b-poly(4-vinylpyridine) (PEG-b-P(4-VP)). The temperature sensor presents both a lower critical response temperature (LCRT) and an upper critical response temperature (UCRT), where the thermoreversible aggregating of PEG-b-P(4-VP) and H2SO4 is used to control the LCRT, and the thermoreversible micellization of PEG-b-PNIPAM is used to control the UCRT. Furthermore, the LCRT can be altered by changing the H2SO4 concentration, and the UCRT can be adjusted by altering the PEG-b-PNIPAM concentration. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3144–3148, 2006
Co-reporter:Linqi Shi;Lichao Gao;Wangqing Zhang;Yingli An;Xiaowei Jiang
Macromolecular Chemistry and Physics 2006 Volume 207(Issue 5) pp:521-527
Publication Date(Web):1 MAR 2006
DOI:10.1002/macp.200500496
Summary: The pH response of the micelles of polystyrene-block-poly(acrylic acid) (PS200-b-PAA78) in water is studied using a combination of techniques: static light scattering (SLS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The structure of the micelles in dilute aqueous solution is dependent on pH. At pH values <2.5, the micelles precipitate. At pH values from 2.5 to 3.5, the micelles associate to form micellar clusters. At pH values ranging from 3.5 to 8.0, the micelles are dynamically frozen. At pH > 8.1, some PS200-b-PAA78 unimers gradually escape from the micelles and subsequently re-associate to form smaller micelles.
Co-reporter:Guiying Li ;Rujiang Ma;Yingli An;Nan Huang
Angewandte Chemie International Edition 2006 Volume 45(Issue 30) pp:
Publication Date(Web):29 JUN 2006
DOI:10.1002/anie.200600172
Getting to the core of the micelle: Phase separation between the hydrophobic shell and the hydrophilic corona leads to channels in the shells of complex micelles (see picture), through which ions and other small molecules could pass. The size of the channels can be regulated by changing the environmental conditions or by manipulating the composition of the two diblock copolymers that form the micelles.
Co-reporter:Guiying Li ;Rujiang Ma;Yingli An;Nan Huang
Angewandte Chemie 2006 Volume 118(Issue 30) pp:
Publication Date(Web):29 JUN 2006
DOI:10.1002/ange.200600172
Ins Innere der Micelle vordringen: Als Folge der Phasentrennung zwischen der hydrophoben Schale und der hydrophilen Korona entstehen in der Schale komplexer Micellen Kanäle (siehe Bild), durch die Ionen und andere kleine Moleküle durchtreten könnten. Die Kanalgröße kann über die Umgebungsbedingungen oder über die Zusammensetzung der beiden Diblockcopolymere, die die Micelle bilden, beeinflusst werden.
Co-reporter:Wangqing Zhang;Lichao Gao;Yingli An;Kai Wu;Lichao Gao;Yingli An;Wangqing Zhang;Kai Wu
Macromolecular Rapid Communications 2005 Volume 26(Issue 16) pp:1341-1345
Publication Date(Web):5 AUG 2005
DOI:10.1002/marc.200500281
Summary: The complexation between polystyrene-block-poly(acrylic acid) (PS-b-PAA) micelles and poly(ethylene glycol)-block-poly(4-vinyl pyridine) (PEG-b-P4VP) is studied, and a facile strategy is proposed to prepare core-shell-corona micellar complexes. Micellization of PS-b-PAA in ethanol forms spherical core-shell micelles with PS block as core and PAA block as shell. When PEG-b-P4VP is added into the core-shell micellar solution, the P4VP block is absorbed into the core-shell micelles to form spherical core-shell-corona micellar complexes with the PS block as core, the combined PAA/P4VP blocks as shell and the PEG block as corona. A model is suggested to characterize the core-shell-corona micellar complexes.
Co-reporter:Kai Wu, Linqi Shi, Wangqing Zhang, Yingli An, Xiao-Xia Zhu, Xu Zhang and Zhanyong Li
Soft Matter 2005 vol. 1(Issue 6) pp:455-459
Publication Date(Web):19 Oct 2005
DOI:10.1039/B512610J
The SO42−-induced micellization of poly(ethylene glycol)-block-poly(4-vinylpyridinium)
(PEG-b-P(4-VPH+)) in aqueous solution is studied by dynamic and static light scattering, and transmission electron microscopy. The SO42− anions can act as cross-linkers of the P(4-VPH+) blocks through the electrostatic attraction between 4-VPH+ and SO42− to induce the micellization of PEG-b-P(4-VPH+). The resultant hybrid micelles are spherical and consist of an ion-complex core of P(4-VPH+)/SO42− and a water-soluble PEG corona and present a density gradient between the core and corona and the core has a higher density. The SO42− concentrations can affect the structure of the core–corona hybrid micelles. The low SO42− conentration leads to a loose core while the high SO42− concentration leads to a compact core.
Co-reporter:Wangqing Zhang;Kai Wu;Z.-J. Miao;Yingli An
Macromolecular Chemistry and Physics 2005 Volume 206(Issue 23) pp:
Publication Date(Web):25 NOV 2005
DOI:10.1002/macp.200590046
Co-reporter:Wangqing Zhang;Z.-J. Miao;Kai Wu;Yingli An
Macromolecular Chemistry and Physics 2005 Volume 206(Issue 23) pp:2354-2361
Publication Date(Web):10 NOV 2005
DOI:10.1002/macp.200500368
Summary: The complexation between polystyrene-block-poly(acrylic acid) (PS-b-PAA) micelles and poly(ethylene glycol)-block-poly(4-vinyl pyridine) (PEG-b-P4VP) is studied and a facile strategy is proposed to prepare three-layered core–shell–corona micellar complexes. Micellization of PS-b-PAA in ethanol gives rise to spherical core–shell micelles with the PS block as the core and the PAA block as the shell. When PEG-b-P4VP is added into the core–shell micellar solution, the P4VP block penetrates into the PAA shell and is absorbed into the core–shell micelles to form spherical core–shell–corona micellar complexes with the PS block as the core, the bonded PAA/P4VP blocks as the shell, and the PEG block as the corona. The core radius, Rc, of the core–shell–corona micellar complexes, 15.1 nm, is equal to that of the core–shell micelles, and the thickness, Ds, of the PEG corona is about 1.5 nm, while the shell thickness, Ds, ranges from 12.2 to 15.7 nm depending on the weight ratio of PEG-b-P4VP to PS-b-PAA.
Co-reporter:Lichao Gao, Linqi Shi, Wangqing Zhang, Yingli An, Xiaowei Jiang, Rujiang Ma and Zhen Liu
Physical Chemistry Chemical Physics 2004 vol. 6(Issue 22) pp:5087-5089
Publication Date(Web):21 Oct 2004
DOI:10.1039/B413703E
Novel microscale layer-by-layer hollow spheres are template-assembled by monodispersed spherical PS-b-PAA micelles during the sublimation of the frozen micellar solution.
Co-reporter:Wangqing Zhang, Linqi Shi, Yingli An, Lichao Gao, Kai Wu, Rujiang Ma and Binglin He
Physical Chemistry Chemical Physics 2004 vol. 6(Issue 1) pp:109-115
Publication Date(Web):26 Nov 2003
DOI:10.1039/B309906G
The self-assembly of polystyrene-b-poly(acrylic acid-co-methyl acrylate)
[PS38-b-P(AA190-co-MA20)] in water was studied. The initial block copolymer concentration greatly influences the morphologies of the resulting aggregates. The morphology of the resulting micelles changes from core–shell spheres with diameter 60 nm to 60–130 nm near-spherical aggregates, and further to 70 nm hollow aggregates, when the initial polymer concentration ranges from 0.20 to 0.50 mg mL−1 and further to 2.0 mg mL−1. The structure of the core–shell spheres and hollow aggregates is further characterized by light scattering. It is found that the core–shell micelles and the hollow aggregates are kinetically frozen in water; the aggregation number of polymer chains Nagg and molecular weight MW of the core–shell micelles and hollow aggregates are relatively large and the solubility of the two morphological micelles in water is poor; the structure of the core–shell spheres is incompact and the hollow aggregates is porous.
Co-reporter:Linqi Shi, Wangqing Zhang, Fenfang Yin, Yingli An, Huan Wang, Lichao Gao and Binglin He
New Journal of Chemistry 2004 vol. 28(Issue 8) pp:1038-1042
Publication Date(Web):13 Jul 2004
DOI:10.1039/B400445K
Amphiphilic block copolymer polystyrene-block-polyacrylic acid (PS-b-PAA) self-assembles into spherical core-shell micelles in the block-selective solvent water with the PS block as the core and the PAA block as the shell. When adding 1-propanol to the micellar solution and then casting the micellar solution at suitable temperatures, the spherical core-shell micelles are assembled into flower-like aggregates on substrates such as glass, formvar film or silicon. The size of the flower-like aggregates ranges from 2×2 µm2 to 15×15 µm2. Casting temperature, substrate type and character of the block copolymers and additive can all affect the assembly of PS-b-PAA micelles. The assembly of micelles is similar to the fractal aggregation of inorganic particles and a possible reason is discussed.
Co-reporter:Wangqing Zhang;Yingli An;Lichao Gao;Kai Wu;Rujiang Ma;Banghua Zhang
Macromolecular Chemistry and Physics 2004 Volume 205(Issue 15) pp:
Publication Date(Web):27 SEP 2004
DOI:10.1002/macp.200400189
Summary: The influence of block-selective solvent on the self-assembly of polystyrene-block-poly[(acrylic acid)-co-(methyl acrylate)] was studied. The nature of the block-selective solvent, which is a binary solvent mixture with different composition, exerts remarkable influence on the morphology of the resulting micelles. When the block-selective solvent is a binary solvent mixture of acetone and water with acetone content ranging from 0 to 90 vol.-%, the resulting aggregates are core-shell spheres with diameter about 60 nm, porous aggregates with diameter of 100, 180 and 250 nm, and core-shell cauliflower-like aggregates with size about 200 nm, respectively. The reason that the morphology of resulting micelles changes with acetone content has been discussed. The structure of the resulting micelles is further characterized in detail by DLS and SLS. Morphological tuning is also achieved by using a binary solvent mixture of ethanol and water or a binary solvent mixture of DMF and water as block-selective solvent. In these cases, core-shell spheres, hollow aggregates, and incompact aggregates are formed with the ethanol or DMF concentration ranging from 10 to 80 vol.-%.
Co-reporter:Aoting Qu, Fan Huang, Ang Li, Huiru Yang, Hao Zhou, Jiafu Long and Linqi Shi
Chemical Communications 2017 - vol. 53(Issue 7) pp:NaN1292-1292
Publication Date(Web):2016/12/21
DOI:10.1039/C6CC07803F
By combining KLVFF peptide and self-assembly chaperone we fabricate a new system to achieve the synchronization between Aβ fibril disaggregation and reducing toxicity of Aβ fragments (monomers or oligomers) that consequently formed. When the KLVFF peptides disaggregate fibrils into fragments, the hydrophobic domains of self-assembly chaperones promptly bind them at the same time. This binding blocks the re-aggregation of the fragments and their interaction with cells, and hence reduces the toxicity of these dangerous fragments.
Co-reporter:Lizhi Zhao, Rui Qu, Ang Li, Rujiang Ma and Linqi Shi
Chemical Communications 2016 - vol. 52(Issue 93) pp:NaN13555-13555
Publication Date(Web):2016/09/15
DOI:10.1039/C6CC05449H
Natural porphyrin derivatives possess many interesting functions in biological systems. They are integrated into proteins that are essential for biological activities. Many efforts have been dedicated to mimic the microenvironment and augment the function of porphyrin/protein scaffolds. To achieve such goals, self-assembly has become one of the popular methods to construct porphyrin/protein-mimicking materials owing to its various choices of building blocks and a simple preparation process over chemical modification. Desirable characteristics of building blocks for protein mimicking include high molecular weight, predictable conformations in solution, and appropriate functional residuals. With these aims in mind, polymers are ideal candidates due to their multiple-level hierarchies derived from their chemical and spatial structures. In this review, design strategies for the cooperative self-assembly of porphyrins with polymers and the main efforts towards the implementation of porphyrin/polymer assembly for biomimetic composites with bioactive functions will be addressed.
Co-reporter:Liangliang Shen, Rui Qu, Hejin Shi, Fan Huang, Yingli An and Linqi Shi
Biomaterials Science (2013-Present) 2016 - vol. 4(Issue 5) pp:NaN862-862
Publication Date(Web):2016/03/24
DOI:10.1039/C6BM00046K
Herein, a complex micelle as an oxygen nano-carrier is constructed through the hierarchical assembly of the diblock copolymer poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLys), tetrakis(4-sulfonatophenyl)porphinato cobalt(II) (Co(II)TPPS), a heptapeptide (Cys-His-His-His-His-His-His) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD). Co(II)TPPS was encapsulated into the cavities of TM-β-CDs driven by the host–guest interaction so that the irreversible formation of a μ-oxo-dimer of Co(II)TPPS can be effectively prevented. The imidazole groups of the heptapeptide were selected as good axial ligands coordinating to the centric cobalt of Co(II)TPPS, which subtly constituted the five-coordinated precursor serving as an active functional centre for oxygen binding. The sixth position of Co(II)TPPS can bind oxygen. Furthermore, the host–guest inclusion (TM-β-CD/Co(II)TPPS) was loaded into the hydrophobic core of the complex micelle and tightly fixed with PLys chains. The hydrophilic PEG blocks stretched in the aqueous solution constitute the shells which stabilize the structure of the complex micelle as well as impart the complex micelle sufficient blood circulation time. Moreover, the complex micelle exhibited excellent biocompatibility and cellular uptake. Therefore, the rationally designed amphiphilic structure can work as promising artificial O2 carriers in vivo. Potentially, the complex micelle can be expected to change the anaerobic microenvironment and find applications in the repair of the cells damaged by cellular hypoxia.
Co-reporter:Liping Chu, Honglin Gao, Tangjian Cheng, Yumin Zhang, Jinjian Liu, Fan Huang, Cuihong Yang, Linqi Shi and Jianfeng Liu
Chemical Communications 2016 - vol. 52(Issue 37) pp:NaN6268-6268
Publication Date(Web):2016/04/04
DOI:10.1039/C6CC01269H
Herein we report on a charge-adaptive nanosystem for prolonged and enhanced in vivo antibiotic delivery. The nanocarrier achieves acid-dependent charge conversion, thus prolonging the circulation time and enhancing antibiotic accumulation in subcutaneous inflammation models.
Co-reporter:Tangjian Cheng, Rujiang Ma, Yumin Zhang, Yuxun Ding, Jinjian Liu, Hanlin Ou, Yingli An, Jianfeng Liu and Linqi Shi
Chemical Communications 2015 - vol. 51(Issue 81) pp:NaN14988-14988
Publication Date(Web):2015/08/11
DOI:10.1039/C5CC05854F
Based on the protonation/deprotonation of poly(β-amino ester) (PAE), mixed-shell micelles (MSMs) with adaptive surfaces could rapidly and reversibly change surface properties to prolong circulation time in blood (pH 7.4) and enhance cellular uptake at tumor sites (pH 6.5).
Co-reporter:Rui Qu, Hejin Shi, Ruolin Wang, Tangjian Cheng, Rujiang Ma, Yingli An and Linqi Shi
Biomaterials Science (2013-Present) 2017 - vol. 5(Issue 3) pp:NaN577-577
Publication Date(Web):2017/01/31
DOI:10.1039/C6BM00813E
Artificial enzymes are widely investigated to mimic the active center and the recognition center of natural enzymes. The active center is responsible for the catalytic activity of enzymes, and the recognition center provides enzymes with specificity. Most of the previous studies on artificial enzymes preferred to solve the problem of activity rather than specificity due to the complexity of the enzyme structures related to substrate recognition. Inspired by the multilevel structures of enzymes and the unique net-structures of hydrogels, hemin-micelles immobilized in alginate hydrogels (HM-AH) were constructed by multistep self-assembly. The hemin-micelle was the active center and mimicked the microenvironment of the catalytic site in horseradish peroxidase (HRP). The alginate hydrogel further enhanced the catalytic activity and stability of hemin-micelles and endowed the artificial enzymes with a catalytic capability in harsh water conditions and non-polar organic solvents. The hydrogel also served as the recognition center, which exhibited substrate selectivity owing to the diffusivity differentiations of substrates in hydrogel fibers. It is the first example of constructing a micelle-hydrogel complex system as an artificial enzyme with both catalytic activity and substrate selectivity by the method of multistep self-assembly.
Co-reporter:Yan Li, Qian Tao, Lizhi Zhao, Rujiang Ma, Yingli An and Linqi Shi
Physical Chemistry Chemical Physics 2010 - vol. 12(Issue 37) pp:NaN11389-11389
Publication Date(Web):2010/08/16
DOI:10.1039/B927056F
To explore the structure and property features of complex aggregates assembled by polymer and organic dye molecules in microcosmic soft confined space, a three-dimensional microconfinement is constructed by W/O inverse emulsion as the site for the complex aggregation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and poly(ethylene glycol)-block-poly(4-vinylpyridine) (PEG-b-P4VP). It is found that porphyrin molecules exist in emulsion droplets mainly as the deprotonated monomer form, even though the pH of the water phase is much lower than the pKa of TPPS in bulk (pKa ≈ 4.7). In spatially confined circumstances, upon blending of the single-component emulsions, complex aggregates are formed due to the thermodynamic collision of emulsion droplets and the subsequent electrostatic interaction between TPPS and polymer. The resultant novel complexes possess a relatively precise structure and homogenous core consisting of a porphyrin and P4VP block. Upon emulsion-breaking, the metastable complex kinetic intermediates generated in original acidic emulsion droplets display a remarkable trend of reaggregation within a certain period of time followed by a disassociation and redispersion. Complex aggregates with some novel morphologies are observed. The final product has a core–shell structure with the electrostatic complex of deprotonized porphyrin molecules homogenously dispersing in the P4VP clew as the core and the soluble PEG as the shell. However, those complexes produced in basic emulsion droplets exhibit a relatively higher stability against further aggregation after breakage of emulsion.
Co-reporter:Qian Tao, Ang Li, Xue Liu, Rujiang Ma, Yingli An and Linqi Shi
Physical Chemistry Chemical Physics 2011 - vol. 13(Issue 36) pp:NaN16271-16271
Publication Date(Web):2011/08/15
DOI:10.1039/C1CP21438A
At high temperature, many enzymes are inactivated by aggregations at hydrophobic sites which are exposed on denaturation. Isolating denatured enzymes via hydrophobic interactions with other material is a significant method to prevent enzymes from aggregation. But the temperature-sensitive polymer poly(N-isopropylacrylamide) (PNIPAAm), supposed to protect enzymes spontaneously at high temperatures, can not efficiently complex denatured carbonic anhydrase B (CAB, as a model enzyme) in bulk aqueous solution due to different phase transition speeds. Here, we present a novel method for protecting enzymes against heat inactivation, in which PNIPAAm and CAB are encapsulated in a confined space constructed by reverse microemulsion. At high temperatures, PNIPAAm forms nanoscale aggregates possessing both large specific surface areas and hydrophobic surfaces, and then adsorbs denatured CABvia hydrophobic interactions to avoid intermolecular aggregation of CAB. With cooling, CAB is released spontaneously and recovers its activity. The assays for enzymatic activity demonstrate that CAB is effectively protected against heat inactivation through this method (protection efficiency is up to 83.2%).
Co-reporter:Xin Wang, Lizhi Zhao, Rujiang Ma, Yingli An and Linqi Shi
Chemical Communications 2010 - vol. 46(Issue 35) pp:NaN6562-6562
Publication Date(Web):2010/08/16
DOI:10.1039/C0CC01674H
Poly(ethyleneglycol)-b-poly(4-vinylpyridine) (PEG-b-P4VP) and zinc meso-5,10,15,20-tetrakis-(4-sulfonatophenyl)porphyrin (ZnTPPS) form complex micelles based on electrostatic interactions. The complex micelles have a core-shell structure that can effectively prevent the demetallization and aggregation of ZnTPPS in acidic aqueous solutions (pH < 4.0).
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