Co-reporter:Jinhui Jiang, Zhibin Zhao, Zijuan Hai, Hongyong Wang, and Gaolin Liang
Analytical Chemistry September 19, 2017 Volume 89(Issue 18) pp:9625-9625
Publication Date(Web):September 6, 2017
DOI:10.1021/acs.analchem.7b02971
The design of tumor-targeting, intracellular protease-activatable near-infrared fluorescence (NIRF) nanoprobes is broadly interesting but remains challenging. In this work, we report the rational design of a NIR probe Cys(StBu)-Lys(Biotin)-Lys-Lys(Cy5.5)-CBT (1) to facilely prepare the self-quenched nanoparticles 1-NPs for tumor-targeted imaging in vitro and in vivo. The biotinylated 1-NPs could be actively uptaken by biotin receptor-overexpressing tumor cells via receptor-mediated endocytosis. Upon intracellular proteolytic cleavage, 1-NPs were disassembled to yield the small molecular probe Lys(Cy5.5)-Luciferin-Lys(Biotin)-Lys-OH (1-D-cleaved), accompanied by fluorescence “Turn-On”. With this NIRF “Turn-On” property, 1-NPs were successfully applied for tumor-targeted imaging. We envision that our nanoparticles could be applied for fluorescence-guided tumor surgery in the near future.
Co-reporter:Ling Dong, Junchao Qian, Zijuan Hai, Jinyong Xu, Wei Du, Kai Zhong, and Gaolin Liang
Analytical Chemistry July 5, 2017 Volume 89(Issue 13) pp:6922-6922
Publication Date(Web):June 19, 2017
DOI:10.1021/acs.analchem.7b00621
Alkaline phosphatase (ALP) is an important enzyme but using ALP-instructed self-assembly of gadolinium nanofibers for enhanced T2-weighted magnetic resonance imaging (MRI) of tumor has not been reported. In this work, we rationally designed a hydrogelator Nap-FFFYp-EDA-DOTA(Gd) (1P) which, under the catalysis of ALP, was able to self-assemble into gadolinium nanofibers to form hydrogel Gel I for enhanced T2-weighted MR imaging of ALP activity in vitro and in tumor. T2 phantom MR imaging indicated that the transverse relaxivity (r2) value of Gel I was 33.9% higher than that of 1P and both of them were 1 order of magnitude higher than that of Gd-DTPA. In vivo T2-weighted MR imaging showed that, at 9.4 T, ALP-overexpressing HeLa tumors of 1P-injected mice showed obviously enhanced T2 contrast. We anticipate that, by replacing ALP with other enzymes, our approach could be applied for MR diagnosis of other diseases in the future.
Co-reporter:Zijuan Hai, Jindan Li, Jingjing Wu, Jiacheng Xu, and Gaolin Liang
Journal of the American Chemical Society 2017 Volume 139(Issue 3) pp:1041-1044
Publication Date(Web):January 8, 2017
DOI:10.1021/jacs.6b11041
Chemiluminescence (CL) has a higher signal-to-noise ratio than fluorescence, but the use of CL to track an enzyme-instructed self-assembly (EISA) process has not been reported. In this work, by coincubation of the hydrogelator precursor Fmoc-Phe-Phe-Tyr(H2PO3)-OH (1P) and the CL agent AMPPD (2) with alkaline phosphatase (ALP), we employed CL to directly characterize and image the simultaneous EISA process of 1P. Hydrogelation processes of 1P with and without 2 and the CL properties of 2 with and without 1P under ALP catalysis were systematically studied. The results indicated that 2 is an ideal CL indicator for ALP-triggered hydrogelation of 1P. Using an IVIS optical imaging system, we obtained time-course CL images of 2 to track the simultaneous hydrogelation process of 1P in the same solution. We envision that our CL method could be employed to track more biological EISA events in the near future.
Co-reporter:Zhen Zheng;Gongyu Li;Chengfan Wu;Miaomiao Zhang;Yue Zhao
Chemical Communications 2017 vol. 53(Issue 25) pp:3567-3570
Publication Date(Web):2017/03/23
DOI:10.1039/C7CC00999B
D-Luciferin is the most widely used substrate for bioluminescence (BL) applications but its low chemical stability always affects its performance. Herein, we rationally designed two chemically stable precursor molecules CBT-D-cystine-CBT (D-1) and CBT-L-cystine-CBT (L-1), and subjected them to reduction-controlled condensation to form 1-oligomer and subsequent proteolysis to yield D-aminoluciferin for BL generation in cells and in vivo. We envision that our precursor molecules might serve as D-luciferin alternatives for a wide range of BL applications in the near future.
Co-reporter:Xiaomei Liu
Chemical Communications 2017 vol. 53(Issue 6) pp:1037-1040
Publication Date(Web):2017/01/17
DOI:10.1039/C6CC09106G
The aggregation-induced emission (AIE) effect has recently been widely applied for biomarker sensing. But developing “smart” strategies to effectively aggregate the AIE fluorogen and additionally enhance the fluorescence emission remain challenging. In this work, by integrating a biocompatible condensation reaction with an AIE fluorogen, we rationally designed a “smart” dual AIE probe Ac-Arg-Val-Arg-Arg-Cys(StBu)-Lys(TPE)-CBT (1) for enhanced fluorescence sensing furin activity in vitro and in living cells. Compared with the single AIE probe Ac-Arg-Val-Arg-Arg-Lys(TPE)-OH (1-Ctrl) which also subjects to furin cleavage, fluorescence emissions of 1 were additionally enhanced 1.7 fold and 3.4 fold in vitro and in living cells, respectively. We envision that, in the near future, our “smart” strategy of enzyme-instructed dual AIE could be widely applied for sensing (or imaging) enzyme activity in vitro and even in vivo with dramatically enhanced sensitivity.
Co-reporter:Zhen Zheng;Peiyao Chen;Gongyu Li;Yunxia Zhu;Zhonghua Shi;Yufeng Luo;Chun Zhao;Ziyi Fu;Xianwei Cui;Chenbo Ji;Fuqiang Wang;Guangming Huang
Chemical Science (2010-Present) 2017 vol. 8(Issue 1) pp:214-222
Publication Date(Web):2016/12/19
DOI:10.1039/C6SC01461E
CBT-Cys click condensation reaction has a high second-order reaction rate constant and has found wide applicability in recent years. However, its reaction mechanism has not been experimentally validated and its application for identifying bioactive N-terminal Cys peptides in real clinical samples has not been reported. Herein, firstly, by employing induced nanoelectrospray ionization-mass spectrometry (InESI-MS) and a home-built micro-reactor, we successfully intercepted and structurally characterized the crucial intermediate in this click reaction for the first time. With the intermediate, the proposed mechanism of this reaction was corroborated. Moreover, we also applied this MS setup to monitor the reaction in real time and obtained the second-order reaction rate constants of this reaction at different pH values. After mechanistic study, we applied this click reaction for identifying bioactive N-terminal cysteine peptides in amniotic fluid (AF). Eight unique N-terminal Cys peptides in AF, three of which are located in the functional domain regions of their corresponding proteins, were identified with a false positive rate less than 1%. One of the three peptides was found able to inhibit the growth of uterine endometrial cancer HEC-1-B cells but not the endometrial normal cells via a typical apoptotic pathway. With its mechanism satisfactorily elucidated, the kinetic parameters obtained, as well as its application for fishing bioactive N-terminal Cys peptides from vast complex clinical samples, we anticipate that this CBT-Cys click reaction could be applied more widely for the facile isolation, site-specific identification, and quantification of N-terminal Cys-containing peptides in complex biological samples.
Co-reporter:Wei Tang;Jingbo Yang;Zhibin Zhao;Zhexiong Lian
Nanoscale (2009-Present) 2017 vol. 9(Issue 45) pp:17717-17721
Publication Date(Web):2017/11/23
DOI:10.1039/C7NR07197C
Dexamethasone (Dex) is one of the essential medicines used to treat inflammation diseases but an overdose of Dex leads to severe adverse effects. The development of a new strategy to boost the anti-inflammation efficacy of Dex is, therefore, important but remains challenging. Herein, by employing an enzyme-instructed self-assembly system, we developed an intracellular coassembly strategy to boost the anti-inflammation efficacy of Dex. Under the catalysis of alkaline phosphatase (ALP), the hydrogelator precursor Nap-Phe-Phe-Tyr(H2PO3)-OH (1p) self-assembled to form Gel 1 but dexamethasone sodium phosphate (Dp) only yielded Dex precipitates. However, subjecting equivalent amounts of 1p and Dp together to ALP-triggered coassembly was found to result in the formation of Gel 2. Cell experiments indicated that intracellular ALP-triggered coassembly of Dp with 1p extensively boosted the anti-inflammation efficacy of Dex on two types inflammatory cell models. We envision that, in the near future, our strategy of intracellular coassembly could be widely employed to boost the therapeutic effects of more drugs, while in the meantime used to alleviate the undesired adverse effects of these drugs.
Co-reporter:Chengfan Wu;Zhen Zheng;Yuenan Guo;Chongli Tian;Qiang Xue
Nanoscale (2009-Present) 2017 vol. 9(Issue 32) pp:11429-11433
Publication Date(Web):2017/08/17
DOI:10.1039/C7NR02499A
When supramolecular hydrogels are applied as tissue culture scaffolds, their mechanical strength and biocompatibility are the two most important factors that must be considered. However, systematic studies on the structure–mechanical property (or structure–cytotoxicity) relationship of hydrogels are rare. Herein, we rationally designed three hydrogelators and their corresponding phosphate precursors, and systematically studied their self-assembling ability and cytotoxicity. The results indicated that fluorine substitution, but not trifluoromethyl substitution with more fluorine atoms, to the phenylalanine motif enhanced the self-assembling ability and cytotoxicity of the hydrogelators (or precursors). We envision that our preliminary study of hydrogelator fluorination would provide a strategy for the development of supramolecular hydrogels for wider biomedical applications.
Co-reporter:Wei Tang;Jingbo Yang;Yue Yuan;Zhibin Zhao;Zhexiong Lian
Nanoscale (2009-Present) 2017 vol. 9(Issue 19) pp:6529-6536
Publication Date(Web):2017/05/18
DOI:10.1039/C6NR09895A
A high concentration of paclitaxel (PTX) is used as an anti-tumor chemotherapy but is toxic to immune cells. At lower concentrations, PTX was found able to stimulate the anti-tumor potentials of immune cells. Thus, decreasing the cytotoxicity of PTX at high concentration while maintaining its anti-tumor stimulation to immune cells remains challenging. Herein, by employing a click condensation reaction, we rationally designed a PTX derivative, Cys(StBu)-Arg-Arg-Arg-Lys(PTX)-CBT (1), for the facile preparation of its nanoparticle 1-NP. In vitro assays indicated that, at high PTX concentrations, 1-NP showed significantly lower cytotoxicity to macrophages than did PTX, and could be efficiently phagocytosed by macrophages and consequently polarize the cells into an anti-tumor state in a dose-dependent manner. In vivo experiments further confirmed that 1-NP had a higher anti-tumor efficacy than did free PTX but lower cytotoxicity to immune cells in both immune organs and tumor sites. Our results suggest that, by using different doses of 1-NP, patients can precisely regulate the activation of the immune system for an effective anti-tumor and balanced autoimmune responses. We also envision that our strategy could lead to a combined use of immunotherapy and chemotherapy for a more efficient anti-tumor treatment in the future.
Co-reporter:Yue Yuan, Zhanling Ding, Junchao Qian, Jia Zhang, Jinyong Xu, Xuejiao Dong, Tao Han, Shuchao Ge, Yufeng Luo, Yuwei Wang, Kai Zhong, and Gaolin Liang
Nano Letters 2016 Volume 16(Issue 4) pp:2686-2691
Publication Date(Web):March 31, 2016
DOI:10.1021/acs.nanolett.6b00331
Large magnetic nanoparticles or aggregates are advantageous in their magnetic resonance properties over ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs), but the former are cleared faster from the blood pool. Therefore, the “smart” strategy of intracellular aggregation of USPIO NPs is required for enhanced T2-weighted MR imaging. Herein, employing an enzyme-instructed condensation reaction, we rationally designed a small molecule Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys-CBT (1) to covalently modify USPIO NPs to prepare monodispersive Fe3O4@1 NPs. In vitro results showed that Fe3O4@1 NPs could be subjected to caspase 3 (Casp3)-instructed aggregation. T2 phantom MR imaging showed that the transverse molar relaxivity (r2) of Fe3O4@1 NPs with Casp3 or apoptotic HepG2 cells was significantly larger than those of control groups. In vivo tumor MR imaging results indicated that Fe3O4@1 NPs could be specifically applied for enhanced T2 MR imaging of tumor apoptosis. We propose that the enzyme-instructed intracellular aggregation of Fe3O4 NPs could be a novel strategy for the design of “smart” probes for efficient T2 MR imaging of in vivo biomarkers.
Co-reporter:Zhen Zheng, Peiyao Chen, Maolin Xie, Chengfan Wu, Yufeng Luo, Wentao Wang, Jun Jiang, and Gaolin Liang
Journal of the American Chemical Society 2016 Volume 138(Issue 35) pp:11128-11131
Publication Date(Web):August 17, 2016
DOI:10.1021/jacs.6b06903
Employing cellular environment for the self-assembly of supramolecular nanofibers for biological applications has been widely explored. But using one precursor to differentiate the extra- and intracellular environments to self-assemble into two different nanofibers remains challenging. With the knowledge that the extracellualr environment of some cancer cells contains large amounts of alkaline phosphatase (ALP) while their intracellular environment is glutathione (GSH)-abundant in mind, we rationally designed a precursor Cys(SEt)-Glu-Tyr(H2PO3)-Phe-Phe-Gly-CBT (1) that can efficiently yield amphiphilic 2 and 2-D to self-assemble into two different nanofibers in hydrogels under the sequential treatment of ALP and GSH. We envision that, by employing a click condensation reaction, this work offers a platform for facilely postmodulation of supramolecular nanofibers, and the versatile precursor 1 could be used to kill two birds with one stone.
Co-reporter:Shuang Liu, Yufeng Luo and Gaolin Liang
Nanoscale 2016 vol. 8(Issue 2) pp:766-769
Publication Date(Web):03 Dec 2015
DOI:10.1039/C5NR07179H
Methylglyoxal (MGO) is a toxic, dicarbonyl metabolite in all living cells and its detoxification is regulated by glyoxalase I (GLOI). Herein, we rationally designed a precursor o-phenylenediamine-Phe-Phe-OH (1) which “click” reacts with MGO to yield amphiphilic methylquinoxaline-Phe-Phe-OH (2) to self-assemble into supramolecular hydrogel II (Gel II). Cryo-TEM images of Gel II suggested that there existed two orders of self-assembly to form the 32.8 nm width-nanotubes in the hydrogel. The hypothesis was validated with the analyses of the fluorescence, transmittance, and circular dichroism data of the serial dilutions of Gel II. Interference tests indicated that hydrogelation of 1 with MGO would not be affected by nitric oxide (NO). Our results suggest that 1 could be applied for specific hydrogelation with MGO, and potentially the removal of MGO in vitro.
Co-reporter:Anming Tang, Yu Qian, Shuang Liu, Weijuan Wang, Bing Xu, An Qin and Gaolin Liang
Nanoscale 2016 vol. 8(Issue 20) pp:10570-10575
Publication Date(Web):28 Apr 2016
DOI:10.1039/C6NR00843G
Osteoporosis (OP) is an important aging-related disease and the effective prevention/treatment of this disease remains challenging. Considering the acidic microenvironment of bone resorption lacunae, herein, we rationally designed two pamidronate (Pami)-derivative and alendronate (Alen)-derivative hydrogelators Pami-D and Alen-D which self-assemble into nanofibers to form supramolecular hydrogels under acidic conditions. Cell viability assay, osteoclastogenesis, osteoclastic gene expression, and in vitro bone resorption results indicated that both Pami-D and Alen-D have better inhibitory effects on osteoclastic formation and bone resorption than Pami and Alen, respectively. We anticipate that our new drugs Pami-D and Alen-D could “smartly” self-assemble and locally concentrate the drugs at bone resorption lacunae in vivo and subsequently prevent/treat osteoporosis more efficiently.
Co-reporter:Fenfen Li, Debo Zhi, Yufeng Luo, Jiqian Zhang, Xiang Nan, Yunjiao Zhang, Wei Zhou, Bensheng Qiu, Longping Wen and Gaolin Liang
Nanoscale 2016 vol. 8(Issue 25) pp:12826-12833
Publication Date(Web):31 May 2016
DOI:10.1039/C6NR02620F
T
1–T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1–T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1–T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1–T2 dual-modal CAs and their application for enhanced T1–T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM−1 s−1 and an r2 value of 186.51 mM−1 s−1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1–T2 dual modal MR CAs for a wide range of theranostic applications in the near future.
Co-reporter:Zhen Zheng, Jihao Wang, Peiyao Chen, Maolin Xie, Lei Zhang, Yubin Hou, Xin Zhang, Jun Jiang, Junfeng Wang, Qingyou Lu and Gaolin Liang
Nanoscale 2016 vol. 8(Issue 33) pp:15142-15146
Publication Date(Web):28 Jul 2016
DOI:10.1039/C6NR03056D
Self-assembly/disassembly is ubiquitous in nature and plays an important role in many biological events. But noninvasive characterization of this process in real time at molecular resolution remains challenging. Herein, using homebuilt liquid-phase scanning tunneling microscopy (L-STM) with ultrahigh stability, we directly visualized enzymatic self-assembly/disassembly of oligopeptide nanofibers in real time for the first time. Static high-resolution L-STM images clearly showed the molecular packing details in the supramolecular nanofiber and the diameter of the nanofiber was consistent with that of cryo transmission electron microscopy (cryo-TEM) observations. Moreover, the self-repairing behavior of the supramolecular nanofibers was also directly observed at high resolution for the first time. This work unprecedentedly revealed new insights into Nature-mimic self-assembly and disassembly at the molecular level. It also illustrates the potential of our homebuilt L-STM in studying delicate biological processes in physiological solution with high resolution.
Co-reporter:Zhen Zheng, Hongbin Sun, Chen Hu, Gongyu Li, Xiaomei Liu, Peiyao Chen, Yusi Cui, Jing Liu, Junfeng Wang, and Gaolin Liang
Analytical Chemistry 2016 Volume 88(Issue 6) pp:3363
Publication Date(Web):February 22, 2016
DOI:10.1021/acs.analchem.6b00036
Tyrosine kinase and phosphatase are two important, antagonistic enzymes in organisms. Development of noninvasive approach for sensing their activity with high spatial and temporal resolution remains challenging. Herein, we rationally designed a hydrogelator Nap-Phe-Phe(CF3)-Glu-Tyr-Ile-OH (1a) whose supramolecular hydrogel (i.e., Gel 1a) can be subjected to tyrosine kinase-directed disassembly, and its phosphate precursor Nap-Phe-Phe(CF3)-Glu-Tyr(H2PO3)-Ile-OH (1b), which can be subjected to alkaline phosphatase (ALP)-instructed self-assembly to form supramolecular hydrogel Gel 1b, respectively. Mechanic properties and internal fibrous networks of the hydrogels were characterized with rheology and cryo transmission electron microscopy (cryo-TEM). Disassembly/self-assembly of their corresponding supramolecular hydrogels conferring respective “On/Off” 19F NMR/MRI signals were employed to sense the activity of these two important enzymes in vitro and in cell lysates for the first time. We anticipate that our new 19F NMR/magnetic resonance imaging (MRI) method would facilitate pharmaceutical researchers to screen new inhibitors for these two enzymes without steric hindrance.
Co-reporter:Xiaomei Liu, Shuang Liu and Gaolin Liang
Analyst 2016 vol. 141(Issue 8) pp:2600-2605
Publication Date(Web):18 Mar 2016
DOI:10.1039/C6AN00110F
Nitric oxide (NO) is the first ubiquitous signaling molecule in the human body. The selective and sensitive detection of NO in vitro and in vivo is of high importance but remains challenging. Previous fluorescent probes for NO detection either are of poor water solubility or lack selectivity over intracellular biomolecules. Herein, we rationally designed a water-soluble, biocompatible, small molecular probe o-phenylenediamine-Phe-Phe-OH (1) for the highly selective and sensitive detection of NO in vitro and in living cells. 1 can react with NO and turn on the fluorescence emission at 367 nm via an ICT mechanism. In vitro tests indicated that 1 showed high selectivity for NO detection without interference from common anions, ROS/RNS, and intracellular biomolecules DHA, AA, or MGO. In PBS buffer, 1 was applied for detecting NO within the range of 0–12 μM with a LOD of 6 nM. Moreover, 1 was successfully applied to sense intracellularly generated NO in living cells. We anticipate that 1 could be potentially employed for studying the toxicity and bioactivity of NO in the near future.
Co-reporter:Zhen Zheng, Anming Tang, Yong Guan, Liang Chen, Fuqiang Wang, Peiyao Chen, Weijuan Wang, Yufeng Luo, Yangchao Tian, and Gaolin Liang
Analytical Chemistry 2016 Volume 88(Issue 24) pp:
Publication Date(Web):December 7, 2016
DOI:10.1021/acs.analchem.6b04139
Alkaline phosphatase (ALP) is an important enzyme, but direct imaging of ALP activity with high spatiotemporal resolution remains challenging. In this work, we rationally designed an iodinated hydrogelator precursor Nap-Phe-Phe(I)-Tyr(H2PO3)-OH (1P) which self-assembles into nanofibers to form hydrogel under the catalysis of ALP. With this property of concentrating iodine atoms at the locations of ALP, 1P was successfully applied for direct nanocomputed tomography (nano-CT) imaging of ALP activity in bacteria for the first time. We envision that, on the basis of this pioneering work, new hydrogelators containing more iodine atoms (e.g., five iodine atoms in 1P) will be designed for better nano-CT imaging of ALP activity with higher CT contrast in the near future.
Co-reporter:Yusi Cui;Wei Du ;Dr. Gaolin Liang
ChemNanoMat 2016 Volume 2( Issue 5) pp:344-353
Publication Date(Web):
DOI:10.1002/cnma.201600052
Abstract
Molecular imaging (MI) plays an important role in both clinical diagnosis and laboratorial research. Developing a “smart” strategy with higher sensitivity for more precise imaging is of great significance but remains challenging. If employed for MI, the self-assembly/disassembly of nanostructures carries five characteristic superiorities in its specific response to a physiological environment: lower toxicity, longer circulating time, higher imaging efficiency, higher signal-to-noise ratio, and ease of functionalization. This review focuses on recent approaches involving the self-assembly/disassembly of nanostructures for the MI of biological events by using different modalities (e.g., magnetic resonance imaging, optical imaging, plasmonic and photoacoustic imaging). We envision that by incorporating multiple imaging modes to the monomer/nanostructures for self-assembly/disassembly, researchers should be able to use this “smart” system for more precise MI in the near future.
Co-reporter:Yue Yuan, Fuqiang Wang, Wei Tang, Zhanling Ding, Lin Wang, Lili Liang, Zhen Zheng, Huafeng Zhang, and Gaolin Liang
ACS Nano 2016 Volume 10(Issue 7) pp:7147
Publication Date(Web):June 27, 2016
DOI:10.1021/acsnano.6b03412
Fatty acid amide hydrolase (FAAH) overexpression induces several disorder symptoms in nerve systems, and therefore long-term tracing of FAAH activity in vivo is of high importance but remains challenging. Current bioluminescence (BL) methods are limited in detecting FAAH activity within 5 h. Herein, by rational design of a latent BL probe (d-Cys-Lys-CBT)2 (1), we developed a “smart” method of intracellular reduction-controlled self-assembly and FAAH-directed disassembly of its cyclic d-luciferin-based nanoparticles (i.e., 1-NPs) for persistent BL imaging of FAAH activity in vitro, in cells, and in vivo. Using aminoluciferin methyl amide (AMA), Lys-amino-d-luciferin (Lys-Luc), and amino-d-luciferin (NH2-Luc) as control BL probes, we validated that the persistent BL of 1 from luciferase-expressing cells or tumors was controlled by the activity of intracellular FAAH. With the property of long-term tracing of FAAH activity in vivo of 1, we envision that our BL precursor 1 could probably be applied for in vivo screening of FAAH inhibitors and the diagnosis of their related diseases (or disorders) in the future.Keywords: bioluminescence; cyclic d-luciferin; disassembly; fatty acid amide hydrolase; self-assembly
Co-reporter:Zhen Zheng, Lin Wang, Wei Tang, Peiyao Chen, Hui Zhu, Yue Yuan, Gongyu Li, Huafeng Zhang, Gaolin Liang
Biosensors and Bioelectronics 2016 Volume 83() pp:200-204
Publication Date(Web):15 September 2016
DOI:10.1016/j.bios.2016.04.067
•A chemosensor was developed for label-free, simple, and fast detection of Cu2+ in aqueous solution with high selectivity.•This D-luciferin derivative chemosensor was applied for specific BL imaging of Cu2+ in tumors.•This work demonstrates the first example of using BL for the in vitro selective detection and intratumoral imaging of a cation.Copper is an essential micronutrient involved in fundamental life processes but using a bioluminescence (BL) probe to selectively sense Cu2+in vitro or image Cu2+in vivo is still unavailable. Herein, a latent BL probe hydrazide d-luciferin (1) was rationally designed and successfully applied it for selective detection of Cu2+in vitro and imaging Cu2+ in living cells and in tumors. Upon the catalysis of Cu2+, 1 was converted to d-luciferin and turned on the BL in the presence of firefly luciferase (fLuc). In vitro tests indicated that 1 could be applied for highly selective sensing Cu2+ within the range of 0–80 μM with a limit of detection (LOD) of 39.0 nM. Cell and animal experiments indicated that 1 could be applied for specific BL imaging of Cu2+ in living cells and tumors and the BL signal of 1 was more stable and longer than that of d-luciferin. We envision that this unique probe 1 might serve as an elucidative tool for further exploration of the biological roles of Cu2+ in physiological and pathological processes in the near future.
Co-reporter:Yue Yuan, Di Li, Jia Zhang, Xianmin Chen, Chi Zhang, Zhanling Ding, Lin Wang, Xueqian Zhang, Junhua Yuan, Yinmei Li, Yanbiao Kang and Gaolin Liang
Chemical Science 2015 vol. 6(Issue 11) pp:6425-6431
Publication Date(Web):28 Jul 2015
DOI:10.1039/C5SC01315A
Cell–cell interactions play a crucial role in the development and function of multicellular organisms. To study cell–cell interactions in vitro, it is a big challenge for researchers to artificially build up cell junctions to bridge different types of cells for this purpose. Herein, by employing two orthogonal click reactions, we rationally designed four click reagents Mal-CBT, Mal-Cys, Mal-Alkyne, and Mal-N3 and successfully applied them to bridge cells of three colors. Orthogonality between these two click reactions was validated in solution and characterized with HPLC and ESI-MS analyses. After modifications of fluorescent protein-expressing prokaryotic Escherichia coli (E. coli) cells (or eukaryotic HEK 293T cells) of three colors with the reagents Mal-Cys, Mal-CBT and Mal-Alkyne, or Mal-N3, the cells were sequentially bridged. The HEK 293T cells showed a higher efficiency of cell bridging than the E. coli cells. Finally, using optical tweezers, we quantitatively measured the bridging probability between Mal-Cys-modified and Mal-CBT-modified HEK 293 cells, as well as the rupture force between two bridged cells. We found that the CBT–Cys click reaction markedly improved the efficiency of cell bridging and the rupture force between two bridged cells was measured to be 153.8 pN at a force-loading rate of 49 pN s−1. Our results demonstrate that it is possible to use two (or n) orthogonal click reactions to bridge three (or n + 1) types of cells. Taking the biological importance of cell junctions into consideration, we anticipate that our method of bridging three types of cells with two bio-orthogonal click reactions will be a useful tool for biologists to study cell–cell interactions with more convenience and efficiency.
Co-reporter:Qingqing Miao, Ziye Wu, Zijuan Hai, Changlu Tao, Qingpan Yuan, Yadi Gong, Yafeng Guan, Jun Jiang and Gaolin Liang
Nanoscale 2015 vol. 7(Issue 6) pp:2797-2804
Publication Date(Web):05 Jan 2015
DOI:10.1039/C4NR06467D
Herein, we report for the first time the use of bipyridine-based hydrogel for selective and visible detection and absorption of Cd2+. At low concentrations, hydrogelator 1 was applied for selective detection of Cd2+in vitro and in living cells with high sensitivity. In the absence of metal ions, 1 is nonfluorescent at 470 nm. Upon addition of metal ions, 1 selectively coordinates to Cd2+, causing an 86-fold increase of fluorescence intensity at 470 nm via the chelation enhanced fluorescence (CHEF) effect, as revealed by first-principles simulations. At 1.5 wt% and pH 5.5, 1 self-assembles into nanofibers to form hydrogel Gel I. Since Cd2+ could actively participate in the hydrogelation and promote the self-assembly, we also successfully applied Gel I for visible detection and absorption of Cd2+. With these excellent properties, Gel I is expected to be explored as one type of versatile biomaterial for not only environmental monitoring but also for pollution treatment in the near future.
Co-reporter:Bin Mei, Qingqing Miao, Anming Tang and Gaolin Liang
Nanoscale 2015 vol. 7(Issue 38) pp:15605-15608
Publication Date(Web):28 Aug 2015
DOI:10.1039/C5NR04563K
Axonal branching is important for vertebrate neuron signaling. Taxol has a biphasic effect on axonal branching (i.e., high concentration inhibits axonal growth but low concentration restores it). To the best of our knowledge, low concentration of taxol to promote axonal branching has not been reported yet. Herein, we rationally designed a taxol derivative Fmoc-Phe-Phe-Lys(taxol)-Tyr(H2PO4)-OH (1) which could be subjected to alkaline phosphatase (ALP)-catalyzed self-assembly to form taxol nanofibers. We found that, at 10 μM, 1 has a microtubule (MT) condensation effect similar to that of taxol on mammalian cells but with more chronic toxicity than taxol on the cells. At a low concentration of 10 nM, 1 not only promoted neurite elongation as taxol did but also promoted axonal branching which was not achieved by using taxol. We propose that self-assembly of 1 along the MTs prohibited their lateral contacts and thus promoted axonal branching. Our strategy of enzyme-instructed self-assembly (EISA) of a taxol derivative provides a new tool for scientists to study the morphology of neurons, as well as their behaviours.
Co-reporter:Qingqing Miao, Chunying Yin, Maolin Xie, Yufeng Luo, Zijuan Hai, Qingpan Yuan, Jun Jiang and Gaolin Liang
Chemical Communications 2015 vol. 51(Issue 55) pp:11045-11047
Publication Date(Web):01 Jun 2015
DOI:10.1039/C5CC02694F
Spontaneously precise organization of small structures into complex superstructures is ubiquitous and important in nature. But using small building blocks to mimic this process remains a challenge to scientists. Herein, we report the rational design of a bipyridine-derivative 1 and applied it for the self-assembly of nanorings. The addition of Fe2+ to the nanorings resulted in the assembly of the nanorings into supernanostructures via Fe2+–bipyridine coordination. HPLC, HR-ESI/MS, UV-vis, DLS, and TEM analyses clearly validated the intramolecular cyclization, self-assembly of the nanorings, and the additional self-assembly of the superstructures via Fe2+–bipyridine coordination. We envision our strategy to be a new approach of precisely assembling nanostructures of ring shape into more complex superstructures.
Co-reporter:Yue Yuan, Jia Zhang, Qinjingwen Cao, Linna An, and Gaolin Liang
Analytical Chemistry 2015 Volume 87(Issue 12) pp:6180
Publication Date(Web):May 19, 2015
DOI:10.1021/acs.analchem.5b01656
There has been no report on enzyme-controlled disassembly of self-quenched NIR fluorescent nanoparticles turning fluorescence on for specific detection/imaging of the enzyme’s activity in vitro and in vivo. Herein, we reported the rational design of new NIR probe 1 whose fluorescence signal was self-quenched upon reduction-controlled condensation and subsequent assembly of its nanoparticles (i.e., 1-NPs). Then disassembly of 1-NPs by furin turned the fluorescence on. Employing this enzymatic strategy, we successfully applied 1-NPs for NIR detection of furin in vitro and NIR imaging furin activity in living cells. Moreover, we also applied 1-NPs for discriminative NIR imaging of MDA-MB-468 tumors in nude mice. This NIR probe 1 might be further developed for tumor-targeted imaging in routine preclinical studies or even in patients in the future.
Co-reporter:Qingqing Miao, Qing Li, Qingpan Yuan, Lingli Li, Zijuan Hai, Shuang Liu, and Gaolin Liang
Analytical Chemistry 2015 Volume 87(Issue 6) pp:3460
Publication Date(Web):February 17, 2015
DOI:10.1021/ac504836a
Simultaneous discriminative sensing of biothiols in vitro and in living cells has remained challenging. Herein, we report a new sulfonamide-based self-quenched fluorescent probe 1 for this purpose with high sensitivity and good selectivity. Treatment of 1 with cysteine (Cys), homocysteine (Hcy), or glutathione (GSH) yields aminoluciferin, 2-cyano-6-aminobenzothiazole homocysteine (CBTHcy), or 2-cyano-6-aminobenzothiazole (CBT), turning “on” the fluorescence at wavelengths of 522, 517, or 490 nm, respectively. Kinetic study indicated that 1 reacts with Cys faster than with Hcy or GSH. With these unique properties of 1, we applied 1 for highly sensitive sensing of Cys, Hcy, and GSH among other 19 natural amino acids (AAs) with good selectivity. Confocal fluorescence microscopic imaging of 1-treated HepG2 cells at two channels (522 ± 8 and 490 ± 8 nm), together with quantitative analysis, indicated that the “turn-on” fluorescence was induced by intracellular Cys-dominating condensation and reduction of 1 but not by intracellular GSH-dominating reduction of 1. This suggests that 1 could be applied for discriminative sensing of intracellular Cys from the abundant GSH. Further development of 1 might bring about an efficient tool for probing cellular functions that relate to biothiols.
Co-reporter:Zijuan Hai, Yajie Bao, Qingqing Miao, Xiaoyi Yi, and Gaolin Liang
Analytical Chemistry 2015 Volume 87(Issue 5) pp:2678
Publication Date(Web):February 12, 2015
DOI:10.1021/ac504536q
Herein, we report a new pyridine-biquinoline-derivative fluorophore L for effectively sensing pyrophosphate (PPi) and monohydrogen sulfide (HS–) in aqueous buffer and in living cells. L could selectively coordinate with metal ions (Mn+) in Groups IB and IIB to form L-Mn+ complexes with 1:1 stoichiometry, resulting in fluorescence quenching via photoinduced electron transfer (PET) mechanism. L-Zn2+ complex was applied to competitively coordinate with PPi to form a new “ate”-type complex, turning on the fluorescence by a 21-fold-increase. The limit of detection (LOD) of this assay for PPi detection in aqueous buffer is 0.85 μM. L-Cu2+ complex was applied for highly selective detection of HS– with an excellent sensitivity by 25-fold decomplexation-induced fluorescence increase. LOD of L-Cu2+ complex for HS– detection in aqueous buffer is 2.24 μM. With the in vitro data obtained, we successfully applied these two complexes for sequential imaging Zn2+ and PPi, Cu2+ and HS– in living cells, respectively. Since PPi and HS– occur in vascular calcification in positive correlation, our multifunctional probe L might help doctors to more precisely diagnose this disease in vivo in the future. For example, we could use radioactive tracer L-64Cu for qualitative and quantitative positron emission tomography/computed tomography (PET/CT) imaging of HS– in vivo.
Co-reporter:Ling Dong, Qingqing Miao, Zijuan Hai, Yue Yuan, and Gaolin Liang
Analytical Chemistry 2015 Volume 87(Issue 13) pp:6475
Publication Date(Web):June 23, 2015
DOI:10.1021/acs.analchem.5b01657
Alkaline phosphatase (ALP)-catalyzed hydrogelation has been extensively explored and found wide applications. Spectroscopic and electrochemical approaches are commonly employed for the detection of ALP activity. Herein, by rational design of a fluorescence probe Fmoc-K(FITC)FFYp (P1) (where FITC is fluorescein), we incorporated sol–gel transition with fluorescence “turn-off” and developed a new method for quantitative sensing ALP activity in vitro and in living cells. Under the catalysis of ALP, P1 was converted to hydrogelator Fmoc-K(FITC)FFY (1) which self-assembles into nanofibers to form Gel I. Accompanying this sol–gel transition, the fluorescence emission of P1 was turned off. Our assay was employed to detect ALP activity over the range of 0–2.8 U/mL with a limit of detection (LOD) of 0.06 U/mL. ALP-inhibitor-treated cell imaging indicated that P1 could be applied for sensing ALP activity in living cells. Our method provides a new option for real time and quantitative sensing ALP activity in vitro and even in living cells.
Co-reporter:Wei Du, Yue Yuan, Lin Wang, Yusi Cui, Hui Wang, Huiqin Xu, and Gaolin Liang
Bioconjugate Chemistry 2015 Volume 26(Issue 12) pp:2571
Publication Date(Web):November 18, 2015
DOI:10.1021/acs.bioconjchem.5b00570
Cancer cell-targeted imaging and drug delivery remain a challenge for precise cancer theranostics. MUC1 is a large transmembrane glycoprotein that may potentially serve as a target for cancer theranostics. Herein, using a MUC1-targeting aptamer (APT) as the “warhead”, we rationally designed and constructed a hybrid nanoparticle 1-NPs-QDs-hAPT (Vehicle) that could be applied for MUC1-targeted cell uptake and imaging. By intercalating different Vehicle amounts with the anticancer drug doxorubicin (DOX), we obtained the multifunctional bioconjugate Vehicle-DOX with a maximized drug payload and DOX fluorescence quenching capability. Confocal microscopy cell imaging indicated that Vehicle-DOX could be used to track MUC1-targeted drug release. A cytotoxicity study indicated that Vehicle-DOX could be applied for MUC1-targeted cytotoxicity. We anticipate that our multifunctional bioconjugate Vehicle-DOX could be applied for in vivo tumor-targeted theranostics.
Co-reporter:Yue Yuan, Shuchao Ge, Hongbin Sun, Xuejiao Dong, Hongxin Zhao, Linna An, Jia Zhang, Junfeng Wang, Bing Hu, and Gaolin Liang
ACS Nano 2015 Volume 9(Issue 5) pp:5117
Publication Date(Web):April 13, 2015
DOI:10.1021/acsnano.5b00287
19F MRI has higher selectivity but lower sensitivity than 1H MRI for in vivo diagnosis. Therefore, to avoid using a high injection dose of the 19F probe while, in the meantime, maintaining the high sensitivity of 19F MRI has remained challenging. Local self-assembly and disassembly of 19F nanoparticles could be one of the “smart” strategies to achieve this goal. Herein, we report a dual-functional probe 1 for glutathione (GSH)-controlled self-assembly and subsequent legumain (Lgmn)-controlled disassembly of its nanoparticles (i.e., 1-NPs). Self-assembly and disassembly of 1-NPs confer 19F magnetic resonance (MR) signals “off” and “on”, respectively. Employing this strategy, we successfully applied 1 for consecutive detections of GSH and Lgmn in vitro and in cells, imaging Lgmn activity in HEK 293T tumors in zebrafish at a low dosage under 14.1 T.Keywords: 19F MRI; disassembly; legumain; self-assembly; zebrafish;
Co-reporter:Yue Yuan, Hongbin Sun, Shuchao Ge, Mengjing Wang, Hongxin Zhao, Lin Wang, Linna An, Jia Zhang, Huafeng Zhang, Bing Hu, Junfeng Wang, and Gaolin Liang
ACS Nano 2015 Volume 9(Issue 1) pp:761
Publication Date(Web):December 29, 2014
DOI:10.1021/nn5062657
Compared to 1H MRI, 19F MRI provides higher selectivity but lower sensitivity. Therefore, the need to inject high doses of the 19F probe to improve its sensitivity for in vivo diagnosis remains a challenge. A “smart” strategy is needed that could locally concentrate a low-dose 19F probe while avoiding the fast transverse relaxation of the probes. Locally self-assembling and disassembling 19F nanoparticles may be an optimal measure to achieve this goal. Herein, we report a dual-functional probe 1 for glutathione (GSH)-controlled self-assembly and subsequent caspase 3/7 (Casp3/7)-controlled disassembly of formed nanoparticles (i.e., 1-NPs). Consecutive assembly and disassembly of 1-NPs translate to “off” and “on” 19F magnetic resonance (MR) signal states, respectively. Employing this smart strategy, we successfully used 1 for the consecutive detection of GSH and Casp3/7 activity in vitro and in cells and imaging Casp3/7 activity in cells and in zebrafish at low doses with a 14.1 T magnetic field.Keywords: 19F MRI; Casp3/7; disassembly; self-assembly; zebrafish;
Co-reporter:Shuang Liu;Anming Tang;Maolin Xie;Yundan Zhao;Dr. Jun Jiang;Dr. Gaolin Liang
Angewandte Chemie International Edition 2015 Volume 54( Issue 12) pp:3639-3642
Publication Date(Web):
DOI:10.1002/anie.201409952
Abstract
Polymer hydrogels and small-molecule-based (SMB) supramolecular hydrogels have been widely explored. But oligomeric hydrogels have remained a challenge because synthetic difficulties of the oligomers and control of their amphiphilicities. Reported herein is the rational design of two precursors Cys(SEt)-Lys-CBT (1) and (Cys-Lys-CBT)2 (2) (CBT=2-cyano-6-aminobenzothiazole) and the use of a biocompatible condensation to prepare oligomeric hydrogels. Glutathione reduction of 1 or 2 yields the same gelator Cys-Lys-CBT (3) which condenses with each other to yield amphiphilic cyclic oligomers. The oligomers instantly self-assemble into nanofibers and form oligomeric hydrogels with similar mechanic properties. Chemical analyses indicated that the major condensation product in both two hydrogels is a cyclic dimer. Considering its biocompatibility, optimal mechanical strength, and biodegradability, we believe that our oligomeric hydrogel might be useful for long-term drug delivery in the future.
Co-reporter:Shuang Liu;Anming Tang;Maolin Xie;Yundan Zhao;Dr. Jun Jiang;Dr. Gaolin Liang
Angewandte Chemie 2015 Volume 127( Issue 12) pp:3710-3713
Publication Date(Web):
DOI:10.1002/ange.201409952
Abstract
Polymer hydrogels and small-molecule-based (SMB) supramolecular hydrogels have been widely explored. But oligomeric hydrogels have remained a challenge because synthetic difficulties of the oligomers and control of their amphiphilicities. Reported herein is the rational design of two precursors Cys(SEt)-Lys-CBT (1) and (Cys-Lys-CBT)2 (2) (CBT=2-cyano-6-aminobenzothiazole) and the use of a biocompatible condensation to prepare oligomeric hydrogels. Glutathione reduction of 1 or 2 yields the same gelator Cys-Lys-CBT (3) which condenses with each other to yield amphiphilic cyclic oligomers. The oligomers instantly self-assemble into nanofibers and form oligomeric hydrogels with similar mechanic properties. Chemical analyses indicated that the major condensation product in both two hydrogels is a cyclic dimer. Considering its biocompatibility, optimal mechanical strength, and biodegradability, we believe that our oligomeric hydrogel might be useful for long-term drug delivery in the future.
Co-reporter:Weijuan Wang, Junchao Qian, Anming Tang, Linna An, Kai Zhong, and Gaolin Liang
Analytical Chemistry 2014 Volume 86(Issue 12) pp:5955
Publication Date(Web):May 23, 2014
DOI:10.1021/ac500967x
Herein, we report, for the first time, the use of MRI methods to study enzymatic hydrogelation. Supramolecular hydrogels have been exploited as biomaterials for many applications. However, behaviors of the water molecules encapsulated in hydrogels have not been fully understood. In this work, we designed a precursor 1 which could self-assemble into nanofibers and form hydrogel I (gel I) upon the catalysis of phosphatase. The differences of mechanic property, pore size, water diffusion rate, and magnetic resonance relaxation times T1 and T2 of gel I containing different concentrations of 1 were systematically studied and analyzed. T1, T2, and diffusion-weighted 1H MR images from gel I phantoms were obtained at 9.4 T. Analyses of the MRI data uncovered how the density of the nanofiber networks affects the relaxation behaviors of the water protons encapsulated in such hydrogels. Rheological analyses and cryo-TEM observations showed increased gel elasticities with increased concentrations of 1 while the pore sizes of gel I decreased. This also resulted in an increase in the proton relaxation rate (i.e., shortened T1, T2, and apparent diffusion coefficient (ADC)) for the water encapsulated in the hydrogel. With MRI, our study provides a new in vitro method to potentially mimic and study in vivo diseases that involve fibrous aggregates.
Co-reporter:Yue Yuan and Gaolin Liang
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 6) pp:865-871
Publication Date(Web):2013/11/07
DOI:10.1039/C3OB41241E
Herein, we review the development, optimization, applications and potential prospects of a novel click reaction based on the condensation reaction between 2-cyanobenzothiazole (CBT) and D-cysteine (D-Cys) in fireflies. This click condensation reaction has obvious advantages in biocompatibility, efficiency and stability in aqueous environments. Optimization of this click reaction has been carried out so that it can be controlled by pH change, reduction, or enzymatic cleavage to synthesize large molecules and self-assembled nanostructures, or enhance probe signals. Consequently, this CBT-based click reaction has been and could be successfully applied to a wide range of biomedical applications such as molecular imaging (e.g., optical imaging, nuclear imaging and magnetic resonance imaging), biomolecular detection, drug delivery and other potentialities.
Co-reporter:Xiaojing Wang, Qingqing Miao, Tingjie Song, Qingpan Yuan, Jinhao Gao and Gaolin Liang
Analyst 2014 vol. 139(Issue 13) pp:3360-3364
Publication Date(Web):17 Apr 2014
DOI:10.1039/C4AN00410H
Herein, we report the development of a new fluorescent switch for sequential and selective sensing of Cu2+ and L-histidine (L-His) in vitro and in living cells for the first time. In the absence of metal ions, Ac-SAACQ-Gly-Gly-Gly-Lys (FITC) (1) exhibits comparable fluorescence to that of free FITC. In the presence of metal ions, 1 selectively coordinates to Cu2+, causing its fluorescence emission to be quenched via photoinduced electron transfer. Interestingly, the as-formed 1–Cu2+ complex selectively responds to L-His among the 20 natural amino acids by turning its fluorescence on. This property of fluorescence switch of 1 was successfully applied for qualitatively and quantitatively sensing Cu2+ and L-His in vitro. Using this dual functional probe, we also sequentially imaged Cu2+ and L-His in living HepG2 cells. Our new probe 1 could be applied for not only environmental monitoring but also biomolecule detection in the near future.
Co-reporter:Yue Yuan, Jia Zhang, Linna An, Qinjingwen Cao, Yun Deng, Gaolin Liang
Biomaterials 2014 35(27) pp: 7881-7886
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.05.071
Co-reporter:Yue Yuan, Shenlong Jiang, Qingqing Miao, Jia Zhang, Mengjing Wang, Linna An, Qinjingwen Cao, Yafeng Guan, Qun Zhang, Gaolin Liang
Talanta 2014 Volume 125() pp:204-209
Publication Date(Web):1 July 2014
DOI:10.1016/j.talanta.2014.02.063
•A water-soluble, biocompatible, fluorescent chemosensor for label-free, simple, and fast detection of Hg2+ in aqueous solution and in cells with high selectivity.•Mechanisms responsible for its fluorescence turn-on effect was gained from ultrafast transient absorption spectroscopy.•A simple device for fast and effective removal of Hg2+ from contaminated water has been constructed.A water-soluble, biocompatible, and fluorescent chemosensor (1) for label-free, simple, and fast detection of mercury ions (Hg2+) in aqueous solutions and in HepG2 cells with high selectivity is reported herein. Chelation of 1 with Hg2+ results in the disappearance of its fluorescence emission at 350 nm and the appearance of a new emission at 405 nm. Selectivity and interference studies indicated that 1 could be selectively chelated by Hg2+ without interference from other metal ions. Insight into the mechanisms responsible for its fluorescence effect was gained from ultrafast transient absorption spectroscopy. With these properties, 1 was successfully applied for imaging Hg2+ in living cells and for removing Hg2+ from river water. Moreover, we also constructed a simple device for fast and effective removal of Hg2+ from contaminated liquid samples.A water-soluble, biocompatible, fluorescent chemosensor for label-free, simple, and fast detection of mercury ions (Hg2+) in aqueous solution and in HepG2 cells with high selectivity was reported. Moreover, a facile device for fast and effective removal of Hg2+ from contaminated liquid samples was also constructed.
Co-reporter:Anming Tang, Bin Mei, Weijuan Wang, Wanglai Hu, Fang Li, Jun Zhou, Qing Yang, Hua Cui, Mian Wu and Gaolin Liang
Nanoscale 2013 vol. 5(Issue 19) pp:8963-8967
Publication Date(Web):01 Aug 2013
DOI:10.1039/C3NR03339B
By employing fluorescence resonance energy transfer (FRET) quenching, we rationally designed two new FITC–quencher based nanoprobes for effectively sensing caspase 3 (Casp3) in vitro and in cells. Our nanoprobes hold promise for assessing the chemotherapeutic effect of cancer treatment.
Co-reporter:Rui Huang, Xijun Wang, Dingli Wang, Fang Liu, Bin Mei, Anming Tang, Jun Jiang, and Gaolin Liang
Analytical Chemistry 2013 Volume 85(Issue 13) pp:6203
Publication Date(Web):June 21, 2013
DOI:10.1021/ac4014012
Herein, we report a new “On–On” strategy based on the assembly and disassembly of fluorescein isothiocyanate nanoparticles (FITC-NPs) for sequential detections of glutathione (GSH) and caspase-3 (Casp3) with a multifunctional fluorescent probe 1. Theoretical investigations revealed the underlying mechanism that satisfactorily explained experimental results of such consecutive enhancements of fluorescence. Using this probe, we also successfully imaged the Casp3 activity in apoptotic cells.
Co-reporter:Yue Yuan, Jia Zhang, Mengjing Wang, Bin Mei, Yafeng Guan, and Gaolin Liang
Analytical Chemistry 2013 Volume 85(Issue 3) pp:1280
Publication Date(Web):January 7, 2013
DOI:10.1021/ac303183v
Taking advantage of a reduction-controlled biocompatible condensation reaction and self-assembly, we have developed a new method for the determination of glutathione (GSH) concentration in vitro and in HepG2 human liver cancer cells. Upon reduction by GSH under physiological conditions (pH 7.4 in buffer), the small molecule CBT-Cys(SEt) condenses and self-assembles into nanorings, increasing the UV absorbance at 380 nm (with significant linear correlation in the 0–87 μM GSH range and a limit of detection of 1 μM). This method is also selective to GSH rather than cysteine in biological samples. Through the use of added internal standards, we successfully determined the concentration of GSH in HepG2 cells to be 14.96 μM (2.99 fmol/cell). To better understand the mechanism of nanoring self-assembly, the condensation product of CBT-Cys(SEt) formed using different concentrations of GSH and different reaction times were characterized by transmission electron microscopy (TEM).
Co-reporter:Qingqing Miao, Xiaoyu Bai, Yingying Shen, Bin Mei, Jinhao Gao, Li Li and Gaolin Liang
Chemical Communications 2012 vol. 48(Issue 78) pp:9738-9740
Publication Date(Web):20 Aug 2012
DOI:10.1039/C2CC34899C
A radioactive probe (1) has been developed and applied to a condensation reaction and self-assembly of radioactive nanoparticles (i.e., 125I-NPs) intracellularly. Upon 160 min cellular efflux, the radioactivity retained in cells incubated with 1 was 4-fold more higher than that of those cells treated with a scrambled control probe (1-Scr).
Co-reporter:Xiaojing Wang, Qian Li, Yue Yuan, Bin Mei, Rui Huang, Ying Tian, Jing Sun, Chunyan Cao, Guangming Lu and Gaolin Liang
Organic & Biomolecular Chemistry 2012 vol. 10(Issue 40) pp:8082-8086
Publication Date(Web):17 Aug 2012
DOI:10.1039/C2OB26279G
Using maleimidoethylmonoamide cysteine (Fmoc)(StBu) (1) as a medium, cysteine residues on proteins of chicken eggshell membrane (ESM) were successfully converted into N-terminal cysteines. After a biocompatible condensation reaction between the N-terminal cysteine and fluorescent probe 2-cyanobenzothiazole-Gly-Gly-Gly-fluorescein isothiocyanate (2), a new fluorogenic structure luciferin-Gly-Gly-Gly-FITC (3) was obtained, which exhibits a 2-fold fluorescence emission increase compared to that of 2. Thus, a new method for effectively labeling cysteine residues on ESMs was developed. Enhanced fluorescence images of ESMs were directly observed under a microscope and a small animal imaging machine.
Co-reporter:Chun-yan Cao, Yue Chen, Fang-zhou Wu, Yun Deng and Gao-lin Liang
Chemical Communications 2011 vol. 47(Issue 37) pp:10320-10322
Publication Date(Web):19 Aug 2011
DOI:10.1039/C1CC14112K
A caspase-3 controlled condensation was applied to self-assemble biotinylated nanoparticles for capturing FITC-labelled streptavidin and subsequently turning on the fluorescence signal.
Co-reporter:Yun Deng, Shuang Liu, Kun Mei, An-ming Tang, Chun-yan Cao and Gao-lin Liang
Organic & Biomolecular Chemistry 2011 vol. 9(Issue 20) pp:6917-6919
Publication Date(Web):15 Aug 2011
DOI:10.1039/C1OB06132A
One multifunctional small molecule can undergo a natural condensation reaction under the control of reducing agent to generate amphiphilic oligomers which quickly self-assemble supramolecular nanoparticles or form crosslinked, reversibly degradable polymers.
Co-reporter:Xiaomei Liu and Gaolin Liang
Chemical Communications 2017 - vol. 53(Issue 6) pp:NaN1040-1040
Publication Date(Web):2016/12/13
DOI:10.1039/C6CC09106G
The aggregation-induced emission (AIE) effect has recently been widely applied for biomarker sensing. But developing “smart” strategies to effectively aggregate the AIE fluorogen and additionally enhance the fluorescence emission remain challenging. In this work, by integrating a biocompatible condensation reaction with an AIE fluorogen, we rationally designed a “smart” dual AIE probe Ac-Arg-Val-Arg-Arg-Cys(StBu)-Lys(TPE)-CBT (1) for enhanced fluorescence sensing furin activity in vitro and in living cells. Compared with the single AIE probe Ac-Arg-Val-Arg-Arg-Lys(TPE)-OH (1-Ctrl) which also subjects to furin cleavage, fluorescence emissions of 1 were additionally enhanced 1.7 fold and 3.4 fold in vitro and in living cells, respectively. We envision that, in the near future, our “smart” strategy of enzyme-instructed dual AIE could be widely applied for sensing (or imaging) enzyme activity in vitro and even in vivo with dramatically enhanced sensitivity.
Co-reporter:Zhen Zheng, Gongyu Li, Chengfan Wu, Miaomiao Zhang, Yue Zhao and Gaolin Liang
Chemical Communications 2017 - vol. 53(Issue 25) pp:NaN3570-3570
Publication Date(Web):2017/03/07
DOI:10.1039/C7CC00999B
D-Luciferin is the most widely used substrate for bioluminescence (BL) applications but its low chemical stability always affects its performance. Herein, we rationally designed two chemically stable precursor molecules CBT-D-cystine-CBT (D-1) and CBT-L-cystine-CBT (L-1), and subjected them to reduction-controlled condensation to form 1-oligomer and subsequent proteolysis to yield D-aminoluciferin for BL generation in cells and in vivo. We envision that our precursor molecules might serve as D-luciferin alternatives for a wide range of BL applications in the near future.
Co-reporter:Zhen Zheng, Peiyao Chen, Gongyu Li, Yunxia Zhu, Zhonghua Shi, Yufeng Luo, Chun Zhao, Ziyi Fu, Xianwei Cui, Chenbo Ji, Fuqiang Wang, Guangming Huang and Gaolin Liang
Chemical Science (2010-Present) 2017 - vol. 8(Issue 1) pp:NaN222-222
Publication Date(Web):2016/08/11
DOI:10.1039/C6SC01461E
CBT-Cys click condensation reaction has a high second-order reaction rate constant and has found wide applicability in recent years. However, its reaction mechanism has not been experimentally validated and its application for identifying bioactive N-terminal Cys peptides in real clinical samples has not been reported. Herein, firstly, by employing induced nanoelectrospray ionization-mass spectrometry (InESI-MS) and a home-built micro-reactor, we successfully intercepted and structurally characterized the crucial intermediate in this click reaction for the first time. With the intermediate, the proposed mechanism of this reaction was corroborated. Moreover, we also applied this MS setup to monitor the reaction in real time and obtained the second-order reaction rate constants of this reaction at different pH values. After mechanistic study, we applied this click reaction for identifying bioactive N-terminal cysteine peptides in amniotic fluid (AF). Eight unique N-terminal Cys peptides in AF, three of which are located in the functional domain regions of their corresponding proteins, were identified with a false positive rate less than 1%. One of the three peptides was found able to inhibit the growth of uterine endometrial cancer HEC-1-B cells but not the endometrial normal cells via a typical apoptotic pathway. With its mechanism satisfactorily elucidated, the kinetic parameters obtained, as well as its application for fishing bioactive N-terminal Cys peptides from vast complex clinical samples, we anticipate that this CBT-Cys click reaction could be applied more widely for the facile isolation, site-specific identification, and quantification of N-terminal Cys-containing peptides in complex biological samples.
Co-reporter:Qingqing Miao, Chunying Yin, Maolin Xie, Yufeng Luo, Zijuan Hai, Qingpan Yuan, Jun Jiang and Gaolin Liang
Chemical Communications 2015 - vol. 51(Issue 55) pp:NaN11047-11047
Publication Date(Web):2015/06/01
DOI:10.1039/C5CC02694F
Spontaneously precise organization of small structures into complex superstructures is ubiquitous and important in nature. But using small building blocks to mimic this process remains a challenge to scientists. Herein, we report the rational design of a bipyridine-derivative 1 and applied it for the self-assembly of nanorings. The addition of Fe2+ to the nanorings resulted in the assembly of the nanorings into supernanostructures via Fe2+–bipyridine coordination. HPLC, HR-ESI/MS, UV-vis, DLS, and TEM analyses clearly validated the intramolecular cyclization, self-assembly of the nanorings, and the additional self-assembly of the superstructures via Fe2+–bipyridine coordination. We envision our strategy to be a new approach of precisely assembling nanostructures of ring shape into more complex superstructures.
Co-reporter:Qingqing Miao, Xiaoyu Bai, Yingying Shen, Bin Mei, Jinhao Gao, Li Li and Gaolin Liang
Chemical Communications 2012 - vol. 48(Issue 78) pp:NaN9740-9740
Publication Date(Web):2012/08/20
DOI:10.1039/C2CC34899C
A radioactive probe (1) has been developed and applied to a condensation reaction and self-assembly of radioactive nanoparticles (i.e., 125I-NPs) intracellularly. Upon 160 min cellular efflux, the radioactivity retained in cells incubated with 1 was 4-fold more higher than that of those cells treated with a scrambled control probe (1-Scr).
Co-reporter:Yue Yuan and Gaolin Liang
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 6) pp:NaN871-871
Publication Date(Web):2013/11/07
DOI:10.1039/C3OB41241E
Herein, we review the development, optimization, applications and potential prospects of a novel click reaction based on the condensation reaction between 2-cyanobenzothiazole (CBT) and D-cysteine (D-Cys) in fireflies. This click condensation reaction has obvious advantages in biocompatibility, efficiency and stability in aqueous environments. Optimization of this click reaction has been carried out so that it can be controlled by pH change, reduction, or enzymatic cleavage to synthesize large molecules and self-assembled nanostructures, or enhance probe signals. Consequently, this CBT-based click reaction has been and could be successfully applied to a wide range of biomedical applications such as molecular imaging (e.g., optical imaging, nuclear imaging and magnetic resonance imaging), biomolecular detection, drug delivery and other potentialities.
Co-reporter:Xiaojing Wang, Qian Li, Yue Yuan, Bin Mei, Rui Huang, Ying Tian, Jing Sun, Chunyan Cao, Guangming Lu and Gaolin Liang
Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 40) pp:NaN8086-8086
Publication Date(Web):2012/08/17
DOI:10.1039/C2OB26279G
Using maleimidoethylmonoamide cysteine (Fmoc)(StBu) (1) as a medium, cysteine residues on proteins of chicken eggshell membrane (ESM) were successfully converted into N-terminal cysteines. After a biocompatible condensation reaction between the N-terminal cysteine and fluorescent probe 2-cyanobenzothiazole-Gly-Gly-Gly-fluorescein isothiocyanate (2), a new fluorogenic structure luciferin-Gly-Gly-Gly-FITC (3) was obtained, which exhibits a 2-fold fluorescence emission increase compared to that of 2. Thus, a new method for effectively labeling cysteine residues on ESMs was developed. Enhanced fluorescence images of ESMs were directly observed under a microscope and a small animal imaging machine.
Co-reporter:Yun Deng, Shuang Liu, Kun Mei, An-ming Tang, Chun-yan Cao and Gao-lin Liang
Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 20) pp:NaN6919-6919
Publication Date(Web):2011/08/15
DOI:10.1039/C1OB06132A
One multifunctional small molecule can undergo a natural condensation reaction under the control of reducing agent to generate amphiphilic oligomers which quickly self-assemble supramolecular nanoparticles or form crosslinked, reversibly degradable polymers.
Co-reporter:Yue Yuan, Di Li, Jia Zhang, Xianmin Chen, Chi Zhang, Zhanling Ding, Lin Wang, Xueqian Zhang, Junhua Yuan, Yinmei Li, Yanbiao Kang and Gaolin Liang
Chemical Science (2010-Present) 2015 - vol. 6(Issue 11) pp:NaN6431-6431
Publication Date(Web):2015/07/28
DOI:10.1039/C5SC01315A
Cell–cell interactions play a crucial role in the development and function of multicellular organisms. To study cell–cell interactions in vitro, it is a big challenge for researchers to artificially build up cell junctions to bridge different types of cells for this purpose. Herein, by employing two orthogonal click reactions, we rationally designed four click reagents Mal-CBT, Mal-Cys, Mal-Alkyne, and Mal-N3 and successfully applied them to bridge cells of three colors. Orthogonality between these two click reactions was validated in solution and characterized with HPLC and ESI-MS analyses. After modifications of fluorescent protein-expressing prokaryotic Escherichia coli (E. coli) cells (or eukaryotic HEK 293T cells) of three colors with the reagents Mal-Cys, Mal-CBT and Mal-Alkyne, or Mal-N3, the cells were sequentially bridged. The HEK 293T cells showed a higher efficiency of cell bridging than the E. coli cells. Finally, using optical tweezers, we quantitatively measured the bridging probability between Mal-Cys-modified and Mal-CBT-modified HEK 293 cells, as well as the rupture force between two bridged cells. We found that the CBT–Cys click reaction markedly improved the efficiency of cell bridging and the rupture force between two bridged cells was measured to be 153.8 pN at a force-loading rate of 49 pN s−1. Our results demonstrate that it is possible to use two (or n) orthogonal click reactions to bridge three (or n + 1) types of cells. Taking the biological importance of cell junctions into consideration, we anticipate that our method of bridging three types of cells with two bio-orthogonal click reactions will be a useful tool for biologists to study cell–cell interactions with more convenience and efficiency.
Co-reporter:Chun-yan Cao, Yue Chen, Fang-zhou Wu, Yun Deng and Gao-lin Liang
Chemical Communications 2011 - vol. 47(Issue 37) pp:NaN10322-10322
Publication Date(Web):2011/08/19
DOI:10.1039/C1CC14112K
A caspase-3 controlled condensation was applied to self-assemble biotinylated nanoparticles for capturing FITC-labelled streptavidin and subsequently turning on the fluorescence signal.
![(2,5-DIOXOPYRROLIDIN-1-YL) 2-[4-(2,5-DIOXOPYRROLIDIN-1-YL)OXYCARBONYLPYRIDIN-2-YL]PYRIDINE-4-CARBOXYLATE](http://img.cochemist.com/ccimg/116600/116565-70-9.png)
![(2,5-DIOXOPYRROLIDIN-1-YL) 2-[4-(2,5-DIOXOPYRROLIDIN-1-YL)OXYCARBONYLPYRIDIN-2-YL]PYRIDINE-4-CARBOXYLATE](http://img.cochemist.com/ccimg/116600/116565-70-9_b.png)
![Benzo[d]thiazole-2-carbonitrile](http://img.cochemist.com/ccimg/2700/2602-85-9.png)
![Benzo[d]thiazole-2-carbonitrile](http://img.cochemist.com/ccimg/2700/2602-85-9_b.png)
![3',6'-Dihydroxy-3H-spiro[isobenzofuran-1,9'-xanthen]-3-one](http://img.cochemist.com/ccimg/2400/2321-07-5.png)
![3',6'-Dihydroxy-3H-spiro[isobenzofuran-1,9'-xanthen]-3-one](http://img.cochemist.com/ccimg/2400/2321-07-5_b.png)
![L-Valinamide,N-acetyl-L-a-aspartyl-L-a-glutamyl-N-[(1S)-2-carboxy-1-formylethyl]-](http://img.cochemist.com/ccimg/169400/169332-60-9.png)
![L-Valinamide,N-acetyl-L-a-aspartyl-L-a-glutamyl-N-[(1S)-2-carboxy-1-formylethyl]-](http://img.cochemist.com/ccimg/169400/169332-60-9_b.png)
![L-Cysteine,S-[1-[[(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)methoxy]methyl]-2,5-dioxo-3-pyrrolidinyl]-](http://img.cochemist.com/ccimg/124600/124505-88-0.png)
![L-Cysteine,S-[1-[[(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)methoxy]methyl]-2,5-dioxo-3-pyrrolidinyl]-](http://img.cochemist.com/ccimg/124600/124505-88-0_b.png)
![L-Alanine, N-[(1,1-dimethylethoxy)carbonyl]-3-(ethyldithio)-](http://img.cochemist.com/ccimg/25500/25461-01-2.png)
![L-Alanine, N-[(1,1-dimethylethoxy)carbonyl]-3-(ethyldithio)-](http://img.cochemist.com/ccimg/25500/25461-01-2_b.png)
