Cell membrane-camouflaged nanoparticles as drug carriers for cancer therapy
作者:
Xu, Cheng-Hui;Ye, Peng-Ju;Zhou, Yang-Chun;He, Dong-Xiu;Wei, Hua* ;...
期刊:
Acta Biomaterialia ,2020年105:1-14 ISSN:1742-7061
通讯作者:
Wei, Hua;Yu, Cui-Yun
作者机构:
[Xu, Cheng-Hui; Wei, Hua; Zhou, Yang-Chun; Ye, Peng-Ju; He, Dong-Xiu; Wei, H; Yu, Cui-Yun] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Xu, Cheng-Hui; Wei, Hua; Zhou, Yang-Chun; Ye, Peng-Ju; He, Dong-Xiu; Yu, Cui-Yun] Univ South China, Inst Pharm Pharmacol, Sch Pharmaceut Sci, Hengyang 421001, Peoples R China.
通讯机构:
[Wei, H; Yu, CY] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
关键词:
Biomimetic nanoparticle;Cancer therapy;Cell membrane;Drug delivery;Nanomedicine
摘要:
The translocation of natural cell membranes to the surface of synthetic nanoparticles, which allows man-made vectors to share merits and functionalities created by nature, has been a hot subject of research in the past decade. The resulting biomimetic nanoparticles not only retain the physicochemical properties of nanomaterials, but also inherit the advantageous functions of source cells. Combined with the preponderances of both synthetic and natural platforms, the optimized biomimetic systems can maximize the drug delivery efficiency. In this review, we first summarize the preparation strategies of the biomimetic systems from the perspective of the correlation between the properties of nanoparticles and cell membranes. Six types of cell membrane-camouflaged nanoparticles are further introduced with an emphasis on their properties and performance. Finally, a concluding remark regarding the primary challenges and opportunities associated with these nanoparticles is presented. Statement of Significance: Translocation of natural cell membranes to the surface of synthetic nanoparticles has been repeatedly highlighted in the past decade to endow man-made vectors with merits and functionalities created by nature; therefore, the resulting biomimetic systems not only retain the physicochemical properties of nanomaterials but also inherit the biological functions of source cells for efficient drug delivery. To provide a timely review on this hot and rapidly developing subject of research, this paper summarized recent progress on the cell membrane-camouflaged nanoparticles as drug carriers for cancer therapy, and focused primarily on six different types of cell membrane-coated nanoparticles with an emphasis on the preparation strategies from the perspective of the correlation between the properties of nanoparticles and cell membrane. © 2020
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英文
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Peptidic Monodisperse PEG "Comb" as Multifunctional "Add-On" Module for Imaging-Traceable and Thermo-Responsive Theranostics.
作者:
Zhu, Junfei;Zhang, Huaibin;Chen, Kexin;Li, Yu;Yang, Zhigang;...
期刊:
Advanced Healthcare Materials ,2020年9(3):e1901331 ISSN:2192-2640
通讯作者:
Jiang, Zhong-Xing
作者机构:
[Jiang, Zhong-Xing; Zhu, Junfei; Zhang, Huaibin; Yang, Zhigang] Wuhan Univ, Sch Pharmaceut Sci, Res Ctr Fluorinated Pharmaceut, Hubei Prov Engn & Technol, Wuhan 430071, Hubei, Peoples R China.;[Li, Yu; Zhou, Xin; Chen, Shizhen; Zhang, Huaibin] Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan, Wuhan 430071, Hubei, Peoples R China.;[Chen, Kexin; Zheng, Xing] Univ South China, Grp Lead Compound, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
通讯机构:
[Jiang, Zhong-Xing] W;Wuhan Univ, Sch Pharmaceut Sci, Res Ctr Fluorinated Pharmaceut, Hubei Prov Engn & Technol, Wuhan 430071, Hubei, Peoples R China.
关键词:
drug delivery;imaging;liposome;polyethylene glycols;stimuli-responsive biomaterials
摘要:
Monodisperse polyethylene glycols-modified (M-PEGylated) biomaterials exhibit high structural accuracy, biocompatibility, and fine-tunable physicochemical properties. To develop "smart" drug delivery systems in a controllable and convenient manner, a peptidic M-PEG "comb" with fluorinated L-lysine side chains and a fluorescent N-terminal is conveniently prepared as a (19) F magnetic resonance imaging ((19) F MRI) and fluorescence dual-imaging traceable and thermo-responsive "add-on" module for liposomal theranostics in cancer therapy. The peptidic M-PEG "comb" has high biocompatibility, thermo-responsivity with a sharp lower critical solution temperature, an aggregation-induced emission fluorescence, and high (19) F MRI sensitivity. As a highly branched amphiphile, it self-assembles and firmly anchors on the doxorubicin-loaded liposomal nanoparticles, which M-PEGylates the liposomes and facilitates the thermo-responsive drug release and drug tracking with dual-imaging technologies. In a rodent xenograft model of human liver cancer HepG2 cells, the M-PEGylated liposomes exhibit long in vivo half time, low toxicity, high tumor accumulation, "hot spot" (19) F MRI, and therapeutic efficacy. With accurately programmable chemical structure, fine-tunable physicochemical and biological properties to meet the demands of diagnosis, drug delivery, and therapy, the M-PEG "comb" is promising as a versatile "add-on" module for rapid and convenient formulation of various "smart" theranostics.
语种:
英文
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Synthesis of a Triple-Responsive Double Hydrophilic Block Copolymer Prodrug Using a Reducible RAFT-ATRP Double-Head Agent
作者:
Sun, Lu;Zhou, Yang;Zhou, Xufeng;Ma, Liwei;Wang, Baoyan;...
期刊:
ACS APPLIED POLYMER MATERIALS ,2020年2(6):2126-2133 ISSN:2637-6105
通讯作者:
Yu, Cuiyun;Wei, Hua
作者机构:
[Wei, Hua; Sun, Lu; Yu, Cuiyun; Wei, H] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wei, Hua; Sun, Lu; Yu, Cuiyun; Wei, H] Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Wei, Hua; Ma, Liwei; Zhou, Yang; Sun, Lu; Wang, Baoyan; Zhou, Xufeng] Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Ma, Liwei; Zhou, Yang; Sun, Lu; Wang, Baoyan; Zhou, Xufeng] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.
通讯机构:
[Yu, CY; Wei, H] U;[Wei, Hua] L;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.
关键词:
DHBC;thermo-sensitivity;reduction-sensitivity;pH sensitivity;polymeric prodrug;RAFT;ATRP
摘要:
Reduction- and acidic-pH-dual-sensitive micelles have been frequently highlighted to present a synergistic effect on the promotion of intracellular drug release for enhanced therapeutic efficiency compared to the delivery systems based on a single biorelevant trigger. However, the preparation of dual-responsive block copolymers with well-defined structures, especially for those with a reducible backbone, are highly desirable for polymer degradation but still suffer from less control, tedious purification, and low efficiency, likely due to the adopted synthetic strategies including various coupling reactions between two polymers. To further develop a versatile route toward well-defined block copolymers with reducible block junctions based on the previously reported RAFT-ATRP double-head agent, 4-cyanopentanoic acid dithio-benzoate-SS-2-hydroxyethyl-2′-(bromoisobutyryl)ethyl disulfide (CPADB-SS-iBuBr), that was only applicable to the glycidyl methacrylate (GMA) monomer, we reported in this study the preparation of a thermo-sensitive double hydrophilic block copolymer (DHBC)-based polymeric prodrug with both a reduction-responsive disulfide link in the backbone and acid-sensitive hydrazone links in the side chainviaa combination of reversible addition-fragmentation chain transfer (RAFT) polymerization, removal of RAFT group, subsequent atom transfer radical polymerization (ATRP), and final drug conjugation. The resulting alkyne-poly(N-(2-hydroxypropyl) methacrylamide-st-(ethyl glycinate methacrylamide-doxorubicin))-SS-poly(N-isopropylacrylamide) (alkyne-P(HPMA-st-(EGMA-DOX))-SS-P(NIPPAm)) can self-assemble into core-shell micelles with an average diameter of 180 nm in water at the physical temperature of 37 °C above the lower critical solution temperature (LCST) of PNIPAAm block. The intracellular simultaneous cleavage of the disulfide links and hydrazone bonds led to significantly promoted degradation of the micelle prodrugs toward accelerated drug release and greater cytotoxicity against cancer cells. Together with the facile decoration of the outer corona of the micelle prodrugs with highly efficient click chemistry, this strategy provides a robust means toward various types of multi-responsive block copolymers for controlled release applications. Copyright © 2020 American Chemical Society
语种:
英文
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Nickel-catalyzed carbodifunctionalization of N-vinylamides enables access to gamma-amino acids
作者:
Yang, Zhi-Fang;Xu, Chang;Zheng, Xing* ;Zhang, Xingang*
期刊:
Chemical Communications ,2020年56(17):2642-2645 ISSN:1359-7345
通讯作者:
Zheng, Xing;Zhang, Xingang
作者机构:
[Yang, Zhi-Fang; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Xu, Chang; Zhang, Xingang] Univ Chinese Acad Sci, Key Lab Organofluorine Chem, Ctr Excellence Mol Synth, Shanghai Inst Organ Chem,Chinese Acad Sci, 345 Lingling Lu, Shanghai 200032, Peoples R China.
通讯机构:
[Zheng, Xing; Zhang, Xingang] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;Univ Chinese Acad Sci, Key Lab Organofluorine Chem, Ctr Excellence Mol Synth, Shanghai Inst Organ Chem,Chinese Acad Sci, 345 Lingling Lu, Shanghai 200032, Peoples R China.
摘要:
A nickel-catalyzed tandem reaction of N-vinylamides with arylboronic acids and bromodifluoroacetate has been developed. The use of amide carbonyl as a chelating group efficiently furnishes a series of protected alpha,alpha-difluoro-gamma-amino acid esters. The reaction can also extend to bromoacetate and 2-bromomalonate. The advantages of this protocol are high functional group tolerance and a broad substrate scope, including a variety of N-vinylamides. In particular, the use of removable amide carbonyl groups provides potential opportunities for applications in peptide chemistry and protein engineering.
语种:
英文
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Platinum (II)-doped graphitic carbon nitride with enhanced peroxidase-like activity for detection of glucose and H2O2
作者:
Zeng, Guo;Duan, Minghui;Xu, Yifan;Ge, Fahuan;Wang, Weiguo*
期刊:
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY ,2020年241:118649 ISSN:1386-1425
通讯作者:
Wang, Weiguo
作者机构:
[Zeng, Guo] Univ South China, Sch Resource Environm & Safety Engn, Hengyang 421000, Hunan, Peoples R China.;[Zeng, Guo; Duan, Minghui] Univ South China, Hengyang Med Coll, Hengyang 421000, Hunan, Peoples R China.;[Wang, Weiguo] Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.;[Xu, Yifan] Guilin Univ Technol, Guilin 541004, Guangxi, Peoples R China.;[Ge, Fahuan] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China.
通讯机构:
[Wang, Weiguo] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.
关键词:
Graphitic carbon nitride;Doped;Nanozyme;Peroxidase-like activity;Glucose detection
摘要:
A platinum (II)-doped graphitic carbon nitride (Pt2+@g-C3N4) nanozyme was prepared in this work. Compared to g-C3N4, Pt2+@g-C3N4 shows enhanced peroxidase-like activity. According to DFT calculations and ESR measurements, the Pt on the surface of g-C3N4 accelerates the decomposition of H2O2 into center dot OH and consequently accelerates TMB oxidation. Furthermore, as a proof of concept, the obtained Pt2+ 2.30@g-C3N4 was applied in the detection of glucose with an LOD of 0.01 mM. The reproducibility and precision tests of the glucose detection method based on Pt-2.30(2+)@g-C3N4 show that this method is reliable and feasible for the detection of glucose. (c) 2020 Elsevier B.V. All rights reserved.
语种:
英文
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A magneto-fluorescence bacteria assay strategy based on dual colour sulfide fluorescent nanoparticles with high near-IR conversion efficiency
作者:
Zhu, Yanli;Wang, Jikai* ;Sun, Yiyang;Cai, Qingyun
期刊:
ANALYST ,2020年145(13):4436-4441 ISSN:0003-2654
通讯作者:
Wang, Jikai
作者机构:
[Cai, Qingyun; Zhu, Yanli; Wang, Jikai] Hunan Univ, State Key Lab Chem Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;[Wang, Jikai] Univ South China, Learning Key Lab Pharmacoprote Hunan Prov, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Sun, Yiyang] China Pharmaceut Univ, Key Lab Biomed Funct Mat, Nanjing 211198, Jiangsu, Peoples R China.
通讯机构:
[Wang, Jikai] U;[Wang, Jikai] H;Univ South China, Learning Key Lab Pharmacoprote Hunan Prov, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;Hunan Univ, State Key Lab Chem Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.
摘要:
Anti-Stokes fluorescence induced by near-IR (NIR) radiation is particularly advantageous for the bioassay of complex samples, but most of the commonly used NIR-induced fluorescence nanomaterials such as up-conversion nanoparticles (UCNPs) do not exhibit satisfactory fluorescence intensity and work against achieving a highly sensitive bioassay. In this study, we a construct sensitive and specific bacteria biosensor based on the NIR-stimulated CaS: Eu, Sm, Mn and SrS: Ce, Sm, Mn nanoparticles. The fluorescent nanoparticles are conjugated with bacteria recognition fragments. In addition, the independent emission bands of these two types of fluorescent nanoparticles make it possible to detect and quantify Gram-positive strain and Gram-negative strain, simultaneously. Intense fluorescence and magnetic enrichment of magneto-fluorescence systems enable bacteria discrimination with the naked eye and improve sensitivity in trace bacteria detection (<20 CFU mL(-1)). The linear relationship between the fluorescence intensity and bacterial concentration is established with a detection range of 25-10(6) CFU mL(-1). Furthermore, this NIR-excited assay strategy demonstrates better anti-interference capability than UV/visible-excited assay methods, showing high potential and practical value for medical diagnostics and bacteria monitoring.
语种:
英文
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Extraction Behavior of Acidic Phosphorus-Containing Compounds to Some Metal Ions: A Combination Research of Experimental and Theoretical Investigations
作者:
Xiang, Ya-Qing;Yao, Xu;Lin, Jin-Hong;Ou, Xiao-Jian;Li, Rong;...
期刊:
JOURNAL OF PHYSICAL CHEMISTRY A ,2020年124(24):5033-5041 ISSN:1089-5639
通讯作者:
Zhou, Yu-Sheng;Yu, Dong-Hai;Xiao, Ji-Chang
作者机构:
[Li, Rong; Yao, Xu; Zhou, Yu-Sheng; Xiang, Ya-Qing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prof Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.;[Lin, Jin-Hong; Yu, Dong-Hai; Xiao, Ji-Chang; Xiang, Ya-Qing] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.;[Ou, Xiao-Jian] Jinchuan Grp, Ltd Laterite Leaching Project Team, Jinchang 737104, Gansu, Peoples R China.
通讯机构:
[Zhou, Yu-Sheng] U;[Yu, DH; Xiao, JC] C;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prof Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.;Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.
会议名称:
75th International Symposium on Molecular Spectroscopy (ISMS)
会议时间:
JUN 22-26, 2020
会议地点:
Champaign Urbana, IL
会议主办单位:
[Xiang, Ya-Qing;Yao, Xu;Li, Rong;Zhou, Yu-Sheng] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prof Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Affiliated Hosp 2, Hengyang 421001, Hunan, Peoples R China.^[Xiang, Ya-Qing;Lin, Jin-Hong;Yu, Dong-Hai;Xiao, Ji-Chang] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China.^[Ou, Xiao-Jian] Jinchuan Grp, Ltd Laterite Leaching Project Team, Jinchang 737104, Gansu, Peoples R China.
关键词:
Chemicals removal (water treatment);Cobalt compounds;Electric batteries;Magnesium compounds;Manganese compounds;Metal ions;Metals;Nickel compounds;Ore treatment;Calculation results;Experimental test;Extractants;Phosphorus-containing compounds;Simplified calculation models;Spent batteries;Theoretical investigations;Valuable metals;Extraction
摘要:
To provide feasible methods for the extraction of valuable metals from spent batteries or low-grade primary ores, the extraction behavior of some representative acidic phosphorus-containing compounds (APCCs) as extractants is evaluated from the perspective of experimental and theoretical investigations in this work. Aqueous solutions containing five metal ions, Ca(II), Co(II), Mg(II), Mn(II), and Ni(II), were made to simulate leaching liquids, and the extraction of these metals was investigated. A simplified calculated model was used to evaluate the interaction between each extractant and metal ions. The calculation results agree well with the experimental tests in trend. This work not only provides potential extractants for the extraction of valuable metals from spent batteries or low-grade primary ores but also demonstrates the practicability of the simplified calculation model. © 2020 American Chemical Society.
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英文
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Surface modification of black phosphorus-based nanomaterials in biomedical applications: Strategies and recent advances
作者:
Zeng, Guodong;Chen, Yuping*
期刊:
Acta Biomaterialia ,2020年118:1-17 ISSN:1742-7061
通讯作者:
Chen, Yuping
作者机构:
[Zeng, Guodong] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.;[Chen, Yuping] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Hunan, Peoples R China.;[Chen, Yuping] Univ South China, Inst Pharm & Pharmacol, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;[Chen, Yuping] Univ South China, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Chen, Yuping] U;Univ South China, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
2D nanomaterials;bioevaluation;black phosphorus;surface modification
摘要:
Black phosphorus-based nanomaterials (BPNMs), an emerging member of two-dimensional (2D) nanomaterials, possess excellent physicochemical properties and hold great potential for application in advanced nanomedicines. However, the bare BPNMs easily decrease their biomedical activities due to their degradability and in vivo interactions with biological macromolecules such as plasma proteins, largely restricting their biomedical application. A variety of surface modifications, via chemical, physical or biological approaches, have been developed for BPNMs to avoid these limitations and achieve stable, long-lasting and safe therapeutic effects, thus enlighten the development of the multifunctional BPNMs for more practical application in the field of biomedicine. The present review summarizes the recent advances in the surface modification of BPNMs and the resultant expansion of their biomedical applications. Focus is put on the strategy and method of modification while the effects incurred on the behavior and potential toxicity of BPNMs are also included. The future and challenge of the surface modification of the therapeutic BPNMs are finally discussed. © 2020
语种:
英文
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Triple Functional AB(2) Unit-Modulated Facile Preparation of Bioreducible Hyperbranched Copolymers
作者:
Liu, Yuping;Cong, Yong;Ma, Wei;Kang, Guiying;Meng, Chao;...
期刊:
ACS BIOMATERIALS SCIENCE & ENGINEERING ,2020年6(5):2812-2821 ISSN:2373-9878
通讯作者:
Yu, Cuiyun;Wei, Hua
作者机构:
[Liu, Yuping; Wei, Hua; Cong, Yong; Ma, Wei; Meng, Chao; Kang, Guiying; Liu, Fangjun] Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Yu, Cuiyun; Wei, H] Univ South China, Dept Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
通讯机构:
[Yu, CY; Wei, H] U;[Wei, Hua] L;Univ South China, Dept Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.
关键词:
AB(2) unit;click coupling;RAFT polymerization;hyperbranched polymer template;controlled drug release
摘要:
Facile preparation of hyperbranched polymers (HPs) has been advanced tremendously by the use of either various multifunctional agent-mediated controlled living radical polymerizations or a highly reactive ABx unit-modulated self-stepwise polymerizations. However, it remains, to our knowledge, a significant challenge to prepare HPs with simultaneously precisely controlled degree of branching (DB) and biorelevant signal-triggered degradation property for controlled release applications due to the respective limitations of the aforementioned two strategies. For this purpose, a triple functional AB2 unit, A-SS-B2 chain transfer agent (AB2 CTA), that integrates the merits of both multifunctional agents and highly reactive ABx units was designed and synthesized successfully to include a disulfide bond for reduction-triggered polymer degradation toward promoted intracellular release of encapsulated cargoes, a trithiocarbonate group for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-based monomer, and three terminal groups consisting of one azide and two alkyne functions for the generation of hyperbranched topology via a self-click coupling-based polymerization. A subsequent self-click polymerization of the resulting AB2 CTA by click coupling in the presence of CuSO4·5H2O and sodium ascorbate (NaVc) generated a hyperbranched polymer template (HPT) with precisely modulated DB and a plurality of CTA units for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-containing monomer. The HPT was next used as a multimacro-CTA for RAFT polymerization of a typical hydrophilic monomer, oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), to demonstrate the potential of this HPT for a robust and facile production of bioreducible hyperbranched polymers for controlled release applications. The synthesized HPT-4-POEGMA can form unimolecular micelles with enhanced stability due to the hyperbranched structure, and the size of micelles varied in the range from 82.4 to 140.3 nm by a modulation of the molar feed ratio of monomer to HPT and polymerization time. More importantly, HPT-POEGMA micelles incubated with 10 mM glutathione (GSH) showed reduction-triggered cleavage of the disulfide links and polymer degradation for promoted intracellular doxorubicin (DOX) release and enhanced therapeutic efficiency. Taken together, this triple functional AB2 CTA provided a powerful means for the facile preparation of bioreducible hyperbranched polymers with precisely controlled DB for controlled release applications. Copyright © 2020 American Chemical Society.
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英文
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Synthesis of polymeric micelles with dual-functional sheddable PEG stealth for enhanced tumor-targeted drug delivery
作者:
Sun, Lu;Wei, Hua* ;Zhang, Xianshuo;Meng, Chao;Kang, Guiying;...
期刊:
Polymer Chemistry ,2020年11(27):4469-4476 ISSN:1759-9954
通讯作者:
Wei, Hua;Yu, Cuiyun
作者机构:
[Wei, Hua; Ma, Wei; Ma, Liwei; Zhang, Xianshuo; Sun, Lu; Wang, Baoyan; Meng, Chao; Kang, Guiying] Lanzhou Univ, Key Lab Nonferrous Met Chem & Resources Utilizat, State Key Lab Appl Organ Chem, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Ma, Wei; Ma, Liwei; Zhang, Xianshuo; Sun, Lu; Wang, Baoyan; Meng, Chao; Kang, Guiying] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Wei, H; Yu, Cuiyun] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wei, Hua; Wei, H; Yu, Cuiyun] Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构:
[Wei, Hua] L;[Wei, H; Yu, CY] U;Lanzhou Univ, Key Lab Nonferrous Met Chem & Resources Utilizat, State Key Lab Appl Organ Chem, Lanzhou 730000, Gansu, Peoples R China.;Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
摘要:
Conjugation of folic acid (FA) onto the surface of nanocarriers for active targeting is the mainstream strategy to improve the targeting efficiency of delivery vehicles for enhanced anticancer drug delivery; however, this strategy suffers from the fast clearance of nanocarriers caused by an immunological response and the nonspecific cellular uptake of nanocarriers compromising therapeutic efficiency and causing serious side effects. To address this dilemma, a dual-functional sheddable monomethoxypolyethylene glycol (mPEG) stealth component for both protection of the FA targeting ligand and extracellular stabilization of the micelles was incorporated into the polymeric micelles to realize simultaneous tumor-triggered targeting and intracellular micelle destabilization for enhanced cellular uptake and drug release. Specifically, the mPEG stealth component containing a tumor acidic pH-cleavable hydrazone bond was linked to an FA-conjugated amphiphilic block-statistical copolymer, FA-poly(oligo(ethylene glycol)monomethyl ether methacrylate)-st-poly(2-hydroxyethyl methacrylate-g-lactide) (P(OEGMA300)-st-P(HEMA-g-LA)) via highly efficient click coupling. The deshielding of the mPEG stealth component at the weakly acidic pH of the tumor site can expose the FA targeting ligand that is shielded under physiological conditions for active targeting, and trigger the destabilization of the self-assembled micelles for accelerated drug release. Meanwhile, reducibly conjugating the FA targeting ligand via a disulfide bond can further promote the targeting efficiency of the micelles by continuous folate receptor (FR)-mediated endocytosis. A panel of block-statistical copolymers with three different hydrophilic weight fractions was synthesized to investigate the structure-property relationship of this micelle construct. The optimized micelle formulation based on mPEG(FA)-P(OEGMA300)4-st-P(HEMA-g-LA)4 is relatively stable at pH 7.4 with a hydrodynamic diameter (Dh) of 41 nm, and the intracellular simultaneous cleavage of the disulfide links and hydrazone bonds led to significantly promoted destabilization of the drug-loaded micelles for promoted drug release. Therefore, the adoption of a sheddable mPEG stealth component with dual functionalities for greater cellular uptake and faster drug release of micelles provides a powerful means of enhanced anticancer drug delivery. © 2020 The Royal Society of Chemistry.
语种:
英文
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Halohydroxylation of alkenyl MIDA boronates: switchable stereoselectivity induced by B(MIDA) substituent
作者:
Zeng, Yao-Fu* ;Liu, Xu-Ge;Tan, Dong-Hang;Fan, Wen-Xin;Li, Yi-Na;...
期刊:
Chemical Communications ,2020年56(31):4332-4335 ISSN:1359-7345
通讯作者:
Zeng, Yao-Fu;Wang, Honggen
作者机构:
[Guo, Yu; Zeng, Yao-Fu; Li, Yi-Na] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;[Wang, Honggen; Liu, Xu-Ge; Fan, Wen-Xin; Tan, Dong-Hang] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China.
通讯机构:
[Zeng, Yao-Fu] U;[Wang, Honggen] S;Univ South China, Inst Pharm & Pharmacol, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Hengyang 421001, Peoples R China.;Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China.
摘要:
The synthesis of α-boryl halohydrins via difunctionalization of alkenyl MIDA boronates has been reported. Intriguing stereoselectivity was found with different halogen sources, which arises from the special stabilizing effect of the B(MIDA) moiety. The transformation provided cis addition products using Cl+ or Br+ as the halogen source, while trans addition products were obtained when I+ was employed. This journal is © The Royal Society of Chemistry.
语种:
英文
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Synthesis of cyclic graft polymeric prodrugs with heterogeneous grafts of hydrophilic OEG and reducibly conjugated CPT for controlled release
作者:
Meng, Chao;Cao, Yufei;Sun, Lu;Liu, Yuping;Kang, Guiying;...
期刊:
BIOMATERIALS SCIENCE ,2020年8(15):4206-4215 ISSN:2047-4830
通讯作者:
Wei, Hua
作者机构:
[Wei, Hua; Meng, Chao] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Thrget New Dr, Hengyang 421001, Peoples R China.;[Wei, Hua; Meng, Chao] Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Liu, Yuping; Wei, Hua; Peng, Jinlei; Ma, Wei; Deng, Kaicheng; Ma, Liwei; Sun, Lu; Meng, Chao; Cao, Yufei; Kang, Guiying] Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.
通讯机构:
[Wei, Hua] U;[Wei, Hua] L;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Thrget New Dr, Hengyang 421001, Peoples R China.;Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.
摘要:
Fabrication of cyclic graft (cg) copolymer-based polymeric prodrugs by conjugation of drug molecules to cg copolymers via a dynamic covalent bond capable of responding to biorelevant signals integrates simultaneously the merits of cg copolymers and polymeric prodrugs for enhanced stability of nanocarriers and precise modulation of drug release kinetics. To completely eliminate the compromised drug conjugation efficiency due to the steric hindrance of hydrophilic grafts, it will be useful to develop cg polymeric prodrugs with heterogeneous grafts composed of hydrophilic polymers and drug species, respectively. For this purpose, we reported in this study the synthesis of cyclic graft polymeric prodrugs with heterogeneous grafts of hydrophilic oligo (ethylene glycol) (OEG) and reducibly conjugated camptothecin (CPT), cg-poly(oligo(ethylene glycol) monomethyl ether methacrylate)-b-poly((2-hydroxyethyl methacrylate)-disulfide link-camptothecin) (cg-P(OEGMA)-b-P(HEMA-SS-CPT), cg-prodrugs), via an integrated strategy of a previously reported diblock copolymer-based template and post-polymerization intermolecular click conjugation of a reducible CPT prodrug. The micelles self-assembled from cg-prodrugs on one hand had sufficient salt stability due to the branched cg structure, and on the other hand showed a reduction-triggered cleavage of the disulfide link for a promoted CPT release. Most importantly, we uncovered two interesting phenomena of the cg-based polymeric prodrugs as delivery vehicles: (i) the dimensions of both self-assemblies formed by the cg and bottlegraft (bg) polymers depend substantially on the molecular size of the cg and bg polymers likely due to the steric hindrance of the grafted structures of the cg and bg molecules and relatively low aggregation number of the self-assembled structures, and (ii) cg-prodrug-based micelles exhibited greater in vitro cytotoxicity against cancer cells despite the lower drug loading content (DLC) than the bg-based analogues, which results primarily from the faster reduction-triggered degradation and drug release as well as the greater cellular uptake efficiency of the former micelle prodrugs. Taken together, the developed cg-prodrugs provide great potential for chemotherapy, and the aforementioned interesting results will definitely inspire more upcoming studies on the future design and development of novel cg polymers for biomedical applications. This journal is © The Royal Society of Chemistry.
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英文
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Facile construction of stabilized, pH-sensitive micelles based on cyclic statistical copolymers of poly(oligo(ethylene glycol)methyl ether methacrylate-st-N,N-dimethylaminoethyl methacrylate) for in vitro anticancer drug delivery
作者:
Zhang, Miao;Liu, Ying;Peng, Jinlei;Liu, Yuping;Liu, Fangjun;...
期刊:
Polymer Chemistry ,2020年11(38):6139-6148 ISSN:1759-9954
通讯作者:
Wei, Hua
作者机构:
[Zhang, Miao; Liu, Yuping; Peng, Jinlei; Wei, Hua; Ma, Wei; Ma, Liwei; Liu, Fangjun] Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.;[Zhang, Miao; Liu, Yuping; Peng, Jinlei; Wei, Hua; Ma, Wei; Ma, Liwei; Liu, Fangjun] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Liu, Ying; Yu, Cui-Yun] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wei, Hua; Liu, Ying; Yu, Cui-Yun] Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构:
[Wei, Hua] L;[Wei, Hua] U;Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.;Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
摘要:
Cyclic polymers have outperformed their linear analogues for controlled release applications in terms of greater stability and better therapeutic efficiency due to the endless chain topology. However, to our knowledge, there have been thus far only a few examples of the fabrication of pH-sensitive cyclic polymers for drug delivery applications. To further improve the colloidal stability of the previously synthesized cyclic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) for drug delivery applications via a facile yet efficient approach, it will be useful and straightforward to incorporate a hydrophilic monomer for copolymerization with DMAEMA. For this purpose, we reported in this study the preparation of pH-sensitive cyclic statistical copolymers, P(OEGMA-st-DMAEMA)s, with two different compositions by atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA) and DMAEMA and subsequent "intra-chain" click cyclization of the a-alkyne-.-azide linear precursor. A further comparison study on the micelle stability revealed that the spherical micelles self-assembled from c-P(OEGMA(4)-st-DMAEMA(38)) (C) with both smaller hydrodynamic size than that of the micelles of the linear analogue, l-P(OEGMA(4)-st-DMAEMA(38)) (L), and greater salt stability than that of the micelles of c-P (OEGMA(8)-st-DMAEMA(38)) were screened to be the optimal micelle construct for drug delivery applications. Flow cytometry (FCM) analysis confirmed greater cellular uptake efficiency of doxorubicin (DOX)loaded C (C@DOX) micelles than that of the L (L@DOX) ones. More importantly, the C@DOX micelles showed comparable in vitro cytotoxicity against the cancer cell line (HeLa cells) but lower in vitro cytotoxicity against the normal cell line (HUVEC cells) relative to the L@DOX formulation after 72 h of incubation. Therefore, this study not only developed a facile approach to improve the colloidal stability of a cyclic polycation, but also presented a pH-sensitive cyclic copolymer-based nanoplatform with great potential for anticancer drug delivery.
语种:
英文
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Delivery of Liver-Specific miRNA-122 Using a Targeted Macromolecular Prodrug toward Synergistic Therapy for Hepatocellular Carcinoma
作者:
Ning, Qjan;Liu, Yu-Feng;Ye, Peng-Ju;Gao, Pei;Li, Zhi-Ping;...
期刊:
ACS Applied Materials & Interfaces ,2019年11(11):10578-10588 ISSN:1944-8244
通讯作者:
Wei, Hua;Yu, Cui-Yun
作者机构:
[Wei, Hua; Li, Zhi-Ping; Ye, Peng-Ju; He, Dong-Xiu; Tang, Si-Yue; Wei, H; Yu, Cui-Yun; Tang, Sheng-Song; Ning, Qjan; Liu, Yu-Feng] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wei, Hua; Li, Zhi-Ping; Ye, Peng-Ju; He, Dong-Xiu; Tang, Si-Yue; Wei, H; Yu, Cui-Yun; Tang, Sheng-Song; Ning, Qjan; Liu, Yu-Feng] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote Hunan Prov, Hengyang 421001, Peoples R China.;[Wei, Hua; Wei, H; Yu, Cui-Yun; Tang, Sheng-Song; Ning, Qjan] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Peoples R China.;[Gao, Pei] Eastern Kentucky Univ, Chem Dept, Richmond, KY 40475 USA.
通讯机构:
[Wei, H; Yu, CY] U;[Wei, H; Yu, CY] H;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote Hunan Prov, Hengyang 421001, Peoples R China.;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Peoples R China.
关键词:
miRNA-122;GC-FU;co-delivery;macromolecular prodrug;hepatocellular carcinoma;synergistic therapy
摘要:
Hepatocellular carcinoma (HCC) poses a great threat to human health. The elegant combination of gene therapy and chemotherapy by nanocarriers has been repeatedly highlighted to realize enhanced therapeutic efficacy relative to monotreatment. However, the leading strategy to achieve the efficient codelivery of the gene and drug remains the electrostatic condensation with the nucleic acid and the hydrophobic encapsulation of drug molecules by the nanocarriers, which suffers substantially from premature drug leakage during circulation and severe off-target-associated side effects. To address these issues, we reported in this study the codelivery of liver-specific miRNA-122 and anti-cancer drug 5-fluorouracil (5-Fu) using a macromolecular prodrug approach, that is, electrostatic condensation with miRNA-122 using galactosylated-chitosan-5-fluorouracil (GC-FU). The delivery efficacy was evaluated comprehensively in vitro and in vivo. Specifically, the biocompatibility of GC-FU/miR-122 nanoparticles (NPs) was assessed by hemolysis activity analysis, BSA adsorption test, and cell viability assay in both normal liver cells (L02 cells) and endothelial cells. The resulting codelivery systems showed enhanced blood and salt stability, efficient proliferation inhibition of HCC cells, and further induction apoptosis of HCC cells, as well as downregulated expression of ADAM17 and Bcl-2. The strategy developed herein is thus a highly promising platform for an effective codelivery of miRNA-122 and 5-Fu with facile fabrication and great potential for the clinical translation toward HCC synergistic therapy. © 2019 American Chemical Society.
语种:
英文
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A pH-sensitive prodrug strategy to co-deliver DOX and TOS in TPGS nanomicelles for tumor therapy
作者:
Xiong, Shujuan;Wang, Zhe;Liu, Juan;Deng, Xiangping;Xiong, Runde;...
期刊:
Colloids and Surfaces B: Biointerfaces ,2019年173:346-355 ISSN:0927-7765
通讯作者:
Tang, Guotao
作者机构:
[Wang, Zhe; Deng, Xiangping; Xie, Zhizhong; Liu, Juan; Lei, Xiaoyong; Xiong, Shujuan; Tang, Guotao; Xiong, Runde; Cao, Xuan] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Xiong, Shujuan] Peoples Hosp Yiyang, Yiyang, Peoples R China.;[Chen, Yanming] Jiuzhitang Co Ltd, Changsha, Hunan, Peoples R China.;[Tang, Guotao] Univ South China, Changsheng Rd 28, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Tang, Guotao] U;Univ South China, Changsheng Rd 28, Hengyang 421001, Hunan, Peoples R China.
关键词:
Co-delivery;Low toxicity;pH-sensitive;Prodrug;Tumor therapy
摘要:
This work has presented a novel strategy for designing pH-sensitive TOS-H-DOX prodrug-loaded TPGS nanomicelles for co-delivery TOS and DOX to enhance tumor therapy and reduce the toxic side effects. DOX was covalently conjugated to the vitamin E succinate through hydrazone bond to produce an pH-sensitive prodrug TOS-H-DOX (amido bond as a control, TOS-A-DOX), which was responsive to the acidic environment in tumor cells, and the prodrugs were subsequently encapsulated in the core of TPGS nanomicelles via hydrophobic effects with a significant drug loading capacity. The pH-sensitive prodrug nanomicelles TOS-H-DOX/TPGS exhibited potent release of DOX in acidic media relative to the pH-insensitive prodrug nanomicelles TOS-A-DOX/TPGS, and further studies of their intracellular uptake and intracellular localization demonstrated that TOS-H-DOX/TPGS nanomicelles can be effectively taken up by cells and drugs can be released. In vitro results confirmed that TOS-H-DOX/TPGS nanomicelles exhibited significant antitumor cell proliferation activity compared to TOS-A-DOX/TPGS and free DOX, TPGS. Furthermore, in vivo studies further confirmed an excellent synergistic antitumor efficacy in MCF-7 tumor-bearing nude mice model. More importantly, the H&E staining of the heart, liver, kidney tissue sections of experimental nude mice showed that TOS-H-DOX/TPGS nanomicelles can reduce damage to them. © 2018 Elsevier B.V.
语种:
英文
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Fabrication of biocleavable crosslinked polyprodrug vesicles via reversible donor–acceptor interactions for enhanced anticancer drug delivery
作者:
Zhang, Xiaolong;Hua, Qi;Meng, Ping;Wang, Mingqi;Wang, Yunfei;...
期刊:
Polymer Chemistry ,2019年10(21):2666-2673 ISSN:1759-9954
通讯作者:
Wei, Hua;Yu, Cuiyun
作者机构:
[Wei, Hua; Hua, Qi; Wang, Yunfei; Ma, Liwei; Sun, Lu; Zhang, Xiaolong; Wang, Baoyan; Wang, Mingqi; Meng, Ping] Lanzhou Univ, Key Lab Nonferrous Met Chem & Resources Utilizat, State Key Lab Appl Organ Chem, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Hua, Qi; Wang, Yunfei; Ma, Liwei; Sun, Lu; Zhang, Xiaolong; Wang, Baoyan; Wang, Mingqi; Meng, Ping] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Yu, Cuiyun; Wei, H] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wei, Hua; Yu, Cuiyun; Wei, H] Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构:
[Wei, Hua] L;[Yu, CY; Wei, H] U;Lanzhou Univ, Key Lab Nonferrous Met Chem & Resources Utilizat, State Key Lab Appl Organ Chem, Lanzhou 730000, Gansu, Peoples R China.;Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
摘要:
Incorporation of various dynamic stimuli-responsive bonds to nanocarriers has been repeatedly highlighted to provide an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficiency; however, most of the developed systems still suffer from drug leakage-associated side effects due to insufficient stability and unsatisfactory therapeutic efficiency attributed to low drug loading capacity. To further address these critical issues, herein we reported a coordination-driven formation of biocleavable crosslinked polyprodrug vesicles (CPV) based on the reversible coordination interactions between the electron acceptor-containing polyprodrug and electron donor-based crosslinker, 1,6-hexanediamine. The resulting CPV exhibited a high drug loading content of 34.8%, and simultaneously enhanced extracellular micelle stability and promoted intracellular redox-triggered decrosslinking and drug release. More importantly, a comparison study further revealed that the CPV outperformed the noncrosslinked analogues in terms of greater stability, faster redox-triggered decrosslinking and drug release, a more compact structure with a smaller size toward higher cellular uptake, and greater in vitro cytotoxicity. This work thus developed a robust reversible crosslinking strategy to address high stability vs. sufficient therapeutic efficiency dilemma of polyprodrug-based nanocarriers.
语种:
英文
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MicroRNA-based potential diagnostic, prognostic and therapeutic applications in triple-negative breast cancer.
作者:
Tang, Qian;Ouyang, Hu;He, Dongxiu* ;Yu, Cuiyun;Tang, Guotao
期刊:
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY ,2019年47(1):2800-2809 ISSN:2169-1401
通讯作者:
He, Dongxiu
作者机构:
[Tang, Qian; Ouyang, Hu; Yu, Cuiyun; Tang, Guotao; He, Dongxiu] Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.;[Yu, Cuiyun; Tang, Guotao; He, Dongxiu] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Hunan, Peoples R China.
通讯机构:
[He, Dongxiu] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421000, Hunan, Peoples R China.
关键词:
Diagnosis;microRNA;prognosis;treatment;triple-negative breast cancer
摘要:
Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer characterized by high recurrence rates and poor prognosis compared to other breast cancers. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of various post-transcriptional gene and silence a broad set of target genes. Many recent studies have demonstrated that miRNAs play an important role in the initiation, promotion, malignant conversion, progression, and metastasis of TNBC. Therefore, the aim of this review is to focus on recent advancements of microRNAs-based potential applications in diagnosis, treatment and prognosis of triple-negative breast cancer. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
语种:
英文
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The fabrication of hybrid micelles with enhanced permeability for drug delivery via a diethoxymethylsilyl-based crosslinking strategy
作者:
Zhang, Xianshuo;Liu, Fangjun;Li, Xiaochen;Tian, Yunfei;Ma, Liwei;...
期刊:
Polymer Chemistry ,2019年10(33):4529-4536 ISSN:1759-9954
通讯作者:
Wei, Hua;Yu, Cuiyun
作者机构:
[Zhang, Xianshuo] Anyang Normal Univ, Sch Chem & Chem Engn, Anyang 455000, Henan, Peoples R China.;[Li, Xiaochen; Wei, Hua; Ma, Liwei; Zhang, Xianshuo; Liu, Fangjun; Tian, Yunfei] Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.;[Li, Xiaochen; Wei, Hua; Ma, Liwei; Zhang, Xianshuo; Liu, Fangjun; Tian, Yunfei] Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;[Wei, Hua; Yu, Cuiyun; Wei, H] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wei, Hua; Yu, Cuiyun; Wei, H] Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构:
[Wei, Hua] L;[Yu, CY; Wei, H] U;Lanzhou Univ, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat, Lanzhou 730000, Gansu, Peoples R China.;Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
摘要:
Crosslinking based on triethoxysilyl-/trimethoxysilyl functionality has been repeatedly highlighted to be the most frequently used strategy for producing crosslinked organic/inorganic hybrid nanovehicles with enhanced stability for drug delivery applications. However, the permeability of the developed nanocarriers is another critical characteristic and should be simultaneously manipulated to realize sufficient release of the loaded therapeutic cargo in order to give an efficient therapeutic dose. The mainstream strategy to control the permeability of a hybrid nanocontainer is probably a modulation of its crosslinking degree via controlled living polymerization techniques. However, this strategy governed from a macromolecular level still suffered from limited and unsatisfactorily regulation. To exert more precise engineering of the permeability of the hybrid nanocarriers at a molecular level, a novel reducible silica monomer, 2-((2-(methacryloyloxy) ethyl)disulfanyl)ethyl (3-(diethoxymethylsilyl)propyl)carbamate (DESSPMA), with diethoxysilyl groups for in situ crosslinking was designed and synthesized in this study, to produce a lower crosslinking density and greater permeability. In addition to a reducible double-head agent comprising a hydroxyl group and a reversible addition-fragmentation chain transfer (RAFT) agent, a dual reduction-sensitive triblock copolymer, poly(ϵ-caprolactone)-SS-poly(DESSPMA)-b-poly(oligoethyleneglycol methacrylate) (PCL-SS-PDESSPMA-b-POEGMA), with disulfide bridges located in both the block junction of the polymer backbone and the side chain containing the crosslinking units was prepared by integrated ring-opening polymerization and RAFT polymerization. Notably, greater drug loading capacity and in vitro cytotoxicity of the DESSPMA-based shell crosslinked micelles relative to those of the 2-((2-(methacryloyloxy) ethyl)disulfanyl)ethyl (3-(triethoxysilyl)propyl)carbamate (TESSPMA)-based analogues were realized, which were attributed to the enhanced permeability because of a lower crosslinking density without compromised micelle stability. Therefore the novel diethoxymethylsilyl-based crosslinking strategy developed herein provides a facile and robust route to engineer organic/inorganic hybrid nanocarriers with enhanced therapeutic efficacy. © The Royal Society of Chemistry 2019.
语种:
英文
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Nickel-Catalyzed Difluoroalkylation-Alkylation of Enamides
作者:
Xu, Chang;Yang, Zhi-Fang;An, Lun;Zhang, Xingang*
期刊:
ACS CATALYSIS ,2019年9(9):8224-8229 ISSN:2155-5435
通讯作者:
Zhang, Xingang
作者机构:
[An, Lun; Xu, Chang; Zhang, Xingang] Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem,Ctr Excellence Mol Sy, 345 Lingling Lu, Shanghai 200032, Peoples R China.;[Yang, Zhi-Fang] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, 28 Western Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Zhang, Xingang] U;Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem,Ctr Excellence Mol Sy, 345 Lingling Lu, Shanghai 200032, Peoples R China.
关键词:
cross-coupling;dialkylzinc reagent;fluorine;nickel;tandem reaction
摘要:
Nickel-catalyzed carbodifunctionalization of alkenes is an efficient strategy for the construction of C-C bonds. However, applications of the strategy in dialkylation of alkenes remain underdeveloped due to the difficulties in suppressing competitive side reactions. We now describe a nickel-catalyzed tandem reaction by difluoroalkylation-alkylation of N-vinyl 2-pyrrolidinone with difluoroalkyl bromides and dialkylzinc reagents. The reaction can also extend to N-vinyloxazolidinone and N-vinylacetamide. This carbodifunctionalization reaction proceeds smoothly under mild reaction conditions with good functional group tolerance, providing a straightforward access to gem-difluoroalkylated 2-pyrrolidinone derivatives that are of interest in medicinal chemistry. © 2019 American Chemical Society.
语种:
英文
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Peptidic Monodisperse PEG "combs" with Fine-Tunable LCST and Multiple Imaging Modalities
作者:
Zhu, Junfei;Xiao, Yan;Zhang, Huaibin;Li, Yu;Yuan, Yaping;...
期刊:
Biomacromolecules ,2019年20(3):1281-1287 ISSN:1525-7797
通讯作者:
Jiang, Zhong-Xing
作者机构:
[Li, Yu; Jiang, Zhong-Xing; Zhu, Junfei; Zhang, Huaibin; Yang, Zhigang] Wuhan Univ, Sch Pharmaceut Sci, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Wuhan 430071, Peoples R China.;[Xiao, Yan; Zheng, Xing] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Zhou, Xin; Chen, Shizhen; Yuan, Yaping] Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan, Wuhan 430071, Peoples R China.
通讯机构:
[Jiang, Zhong-Xing] W;Wuhan Univ, Sch Pharmaceut Sci, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Wuhan 430071, Peoples R China.
摘要:
Thermosensitive and imaging-traceable materials with fine-tunable lower critical solution temperature (LCST) around body temperature are highly valuable in biomedicine. However, such materials are rare because it is challenging to fine-tune the LCST and incorporate suitable imaging modalities. Herein, peptidic monodisperse polyethylene glycol (M-PEG) "combs" with fine-tunable LCST, "hot spot" fluorine-19 magnetic resonance imaging ((19)F MRI), thermoresponsive fluorescent imaging, and drug loading ability were developed through accurately programming their structures during solid phase peptide synthesis (SPPS). The easy availability, structural accuracy, biocompatibility, and versatility provide the M-PEG "combs" with promising prospects as thermoresponsive and imaging-traceable biomaterials for controlled drug delivery.
语种:
英文
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