Molecular recognition and photoprotection of riboflavin in water by a biomimetic host
作者:
Zhang, Hong;Wang, Li-Li* ;Pang, Xin-Yu;Yang, Liu-Pan* ;Jiang, Wei*
期刊:
Chemical Communications ,2021年57(100):13724-13727 ISSN:1359-7345
通讯作者:
Wang, Li-Li;Yang, Liu-Pan;Jiang, Wei
作者机构:
[Yang, Liu-Pan; Jiang, Wei; Zhang, Hong; Pang, Xin-Yu; Wang, Li-Li; Yang, LP] Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Guangdong Prov Key Lab Catalysis, Xueyuan Blvd 1088, Shenzhen 518055, Peoples R China.;[Yang, Liu-Pan; Jiang, Wei; Zhang, Hong; Pang, Xin-Yu; Wang, Li-Li; Yang, LP] Southern Univ Sci & Technol, Dept Chem, Xueyuan Blvd 1088, Shenzhen 518055, Peoples R China.;[Wang, Li-Li] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wang, Li-Li] Univ South China, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构:
[Wang, LL; Yang, LP; Jiang, W] S;[Wang, Li-Li] U;Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Guangdong Prov Key Lab Catalysis, Xueyuan Blvd 1088, Shenzhen 518055, Peoples R China.;Southern Univ Sci & Technol, Dept Chem, Xueyuan Blvd 1088, Shenzhen 518055, Peoples R China.;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
摘要:
A water-soluble tetralactam macrocycle with 2,6-diethoxynaphthalene groups as side walls is able to strongly bind riboflavin (Ka>107M−1) in water through hydrogen bonding and the hydrophobic effect. The encapsulated riboflavin can be stabilized by the host against photo-degradation under UV-vis irradiation, which may be harnessed to extend the shelf life of riboflavin. © The Royal Society of Chemistry 2021.
语种:
英文
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Spider Toxin Peptide-Induced NIR Gold Nanocluster Fabrication for GSH-Responsive Cancer Cell Imaging and Nuclei Translocation
作者:
Tan, Huaxin;Liu, Sisi;He, Yaolin;Cheng, Guofeng;Zhang, Yu;...
期刊:
Frontiers in Bioengineering and Biotechnology ,2021年9:780223 ISSN:2296-4185
通讯作者:
Hu, Lidan
作者机构:
[Tan, Huaxin; Hu, Lidan; Zhang, Yu; Cheng, Guofeng] Univ South China, Key Lab Ecol Environm & Crit Human Dis Prevent Hu, Dept Biochem & Mol Biol, Dept Educ,Sch Basic Med,Hengyang Med Sch, Hengyang, Peoples R China.;[Liu, Sisi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang, Peoples R China.;[He, Yaolin] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Radiotherapy, Hengyang, Peoples R China.;[Wei, Xiaojie] Univ South China, Sch Pharm, Hengyang Med Sch, Hengyang, Peoples R China.
通讯机构:
[Hu, Lidan] U;Univ South China, Key Lab Ecol Environm & Crit Human Dis Prevent Hu, Dept Biochem & Mol Biol, Dept Educ,Sch Basic Med,Hengyang Med Sch, Hengyang, Peoples R China.
关键词:
NIR gold nanoclusters;spider toxin peptide;Cancer cell imaging;nuclei translocation;GSH-responsive
摘要:
Goldnanoclusters (GNCs) have become a promising nanomaterial for bioimaging because of their unique optical properties and biocompatibility. In this study, lycosin-I peptide, which possesses a highly selective anticancer activity by affecting the permeability of cancer cell membrane, was firstly modified for constructing fluorescent GNCs (LGNCs) for bioimaging of tumor cells. The obtained LGNCs exhibited strong near-infrared (NIR) fluorescence, which can be further enhanced by the peptide-induced aggregation and selectively stained three cancerous cell lines over normal cell lines with low intrinsic toxicity. After uptake by tumor cells, LGNC aggregates can be depolymerized into ultrasmall nanoclusters by high-level glutathione (GSH) and realize the nuclear targeting translocation. Collectively, our work suggests the potential of natural active biomolecules in designing NIR fluorescent GNCs for bioimaging. Copyright © 2021 Tan, Liu, He, Cheng, Zhang, Wei and Hu.
语种:
英文
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Perfluoro-tert-butanol: a cornerstone for high performance fluorine-19 magnetic resonance imaging
作者:
Wu, Tingjuan;Li, Anfeng;Chen, Kexin;Peng, Xingxing;Zhang, Jing;...
期刊:
Chemical Communications ,2021年57(63):7743-7757 ISSN:1359-7345
通讯作者:
Zheng, Xing(zhengxing9166@sohu.com);Jiang, Zhong-Xing(zxjiang@whu.edu.cn);Zhou, Xin(xinzhou@wipm.ac.cn)
作者机构:
[Peng, Xingxing; Li, Anfeng; Jiang, Zhong-Xing; Wu, Tingjuan; Chen, Kexin; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol New Drug Stud, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Grp Lead Cpd,Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Jing; Jiang, Zhong-Xing] Wuhan Univ, Sch Pharmaceut Sci, Hubei Prov Engn & Technol Res Ctr Fluorinated Pha, Wuhan 430071, Peoples R China.;[Zhou, Xin; Chen, Shizhen; Jiang, Mou] Chinese Acad Sci, Innovat Acad Precis Measurement Sci & Technol, Wuhan Inst Phys & Math, Natl Ctr Magnet Resonance Wuhan,State Key Lab Mag, Wuhan 430071, Peoples R China.
通讯机构:
[Jiang, Zhong-Xing; Wu, Tingjuan] G;[Jiang, Mou] S;[Zhang, Jing] H;Group of Lead Compound, Department of Pharmacy, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, China.;Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
摘要:
As a versatile quantification and tracking technology, 19F magnetic resonance imaging (19F MRI) provides quantitative 'hot-spot'images without ionizing radiation, tissue depth limit, and background interference. However, the lack of suitable imaging agents severely hampers its clinical application. First, because the 19F signals are solely originated from imaging agents, the relatively low sensitivity of MRI technology requires high local 19F concentrations to generate images, which are often beyond the reach of many 19F MRI agents. Second, the peculiar physicochemical properties of many fluorinated compounds usually lead to low 19F signal intensity, tedious formulation, severe organ retention, etc. Therefore, the development of 19F MRI agents with high sensitivity and with suitable physicochemical and biological properties is of great importance. To this end, perfluoro-tert-butanol (PFTB), containing nine equivalent 19F and a modifiable hydroxyl group, has outperformed most perfluorocarbons as a valuable building block for high performance 19F MRI agents. Herein, we summarize the development and application of PFTB-based 19F MRI agents and analyze the strategies to improve their sensitivity and physicochemical and biological properties. In the context of PFC-based 19F MRI agents, we also discuss the challenges and prospects of PFTB-based 19F MRI agents. © 2021 The Royal Society of Chemistry.
语种:
英文
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A tumor microenvironment (TME)-responsive nanoplatform for systemic saporin delivery and effective breast cancer therapy
作者:
Shen, Qian;Xu, Lei;Li, Rong;Wu, Guang;Li, Senlin;...
期刊:
Chemical Communications ,2021年57(20):2563-2566 ISSN:1359-7345
通讯作者:
Li, Rong(l7979r@163.com)
作者机构:
[Zhou, Yusheng; Li, Rong; Xu, Xiaoding; Shen, Qian; Wu, Guang] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Zhou, Yusheng; Li, Rong; Xu, Xiaoding; Shen, Qian; Wu, Guang] Univ South China, Affiliated Hosp 2, Hengyang 421001, Peoples R China.;[Saw, Phei Er; Xu, Xiaoding; Xu, Lei; Li, Senlin] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China.;[Zhou, Yusheng] Univ South China, Affiliated Nanhua Hosp, Hengyang 421001, Peoples R China.
通讯机构:
[Shen, Qian; Zhou, Yusheng; Xu, Xiaoding] I;Institute of Pharmacy & Pharmacology and the Second Affiliated Hospital, University of South China, Hengyang 421001, P. R. China. yszhou08@126.com;Institute of Pharmacy & Pharmacology and the Second Affiliated Hospital, University of South China, Hengyang 421001, P. R. China. yszhou08@126.com and The Affiliated Nanhua Hospital, University of South China, Hengyang 421001, P. R. China. xuxiaod5@mail.sysu.edu.cn;Institute of Pharmacy & Pharmacology and the Second Affiliated Hospital, University of South China, Hengyang 421001, P. R. China. yszhou08@126.com and Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P. R. China
摘要:
Intracellular delivery of therapeutic proteins remains a challenge for the success of protein-mediated disease treatment. We herein develop a robust nanoplatform made with a TME-pH responsive Meo-PEG-b-PPMEMA polymer and a cationic lipid-like compoundG0-C14forin vivodelivery of cytotoxic saporin and breast cancer therapy. This nanoplatform could respond to a TME pH to rapidly release saporin/G0-C14complexes, which could significantly improve the uptake of cytosolic saporin by tumor cells and subsequent endosomal escape, thereby leading to an effective inhibition of tumor growth. © The Royal Society of Chemistry 2021.
语种:
英文
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Highly Sensitive and Specific Mass Spectrometric Platform for miRNA Detection Based on the Multiple-Metal-Nanoparticle Tagging Strategy
作者:
Zhu, Yan-Li;Lian, Yan-Mei;Wang, Ji-Kai;Chen, Zeng-Ping;Yu, Ru-Qin
期刊:
Analytical Chemistry ,2021年93(14):5839-5848 ISSN:0003-2700
通讯作者:
Chen, Zeng-Ping(zpchen@hnu.edu.cn)
作者机构:
[Yu, Ru-Qin; Zhu, Yan-Li; Chen, Zeng-Ping; Lian, Yan-Mei] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;[Wang, Ji-Kai] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构:
[Zeng-Ping Chen] S;State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, P. R. China
摘要:
The multiple-metal-nanoparticle tagging strategy has generally been applied to the multiplexed detection of multiple analytes of interest such as microRNAs (miRNAs). Herein, it was used for the first time to improve both the specificity and sensitivity of a novel mass spectroscopic platform for miRNA detection. The mass spectroscopic platform was developed through the integration of the ligation reaction, hybridization chain reaction amplification, multiple-metal-nanoparticle tagging, and inductively coupled plasma mass spectrometry. The high specificity resulted from the adoption of the ligation reaction is further enhanced by the multiple-metal-nanoparticle tagging strategy. The combination of hybridization chain reaction amplification and metal nanoparticle tagging endows the proposed platform with the feature of high sensitivity. The proposed mass spectrometric platform achieved quite satisfactory quantitative results for Let-7a in real-world cell line samples with accuracy comparable to that of the real-time quantitative reverse-transcriptase polymerase chain reaction method. Its limit of detection and limit of quantification for Let-7a were experimentally determined to be about 0.5 and 10 fM, respectively. Furthermore, due to the unique way of utilizing the multiple-metal-nanoparticle tagging strategy, the proposed platform can unambiguously discriminate between the target miRNA and nontarget ones with single-nucleotide polymorphisms based on their response patterns defined by the relative mass spectral intensities among the multiple tagged metal elements and can also provide location information of the mismatched bases. Its unique advantages over conventional miRNA detection methods make the proposed platform a promising and alternative tool in the fields of clinical diagnosis and biomedical research. ©
语种:
英文
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Recent Progresses in NIR-I/II Fluorescence Imaging for Surgical Navigation
作者:
Li, Songjiao;Cheng, Dan;He, Longwei* ;Yuan, Lin
期刊:
Frontiers in Bioengineering and Biotechnology ,2021年9:768698 ISSN:2296-4185
通讯作者:
He, Longwei
作者机构:
[He, Longwei; Li, Songjiao] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Dept Pharm & Pharmacol, Canc Res Inst,Hengyang Med Sch,Affiliated Hosp 1, Hengyang, Peoples R China.;[Cheng, Dan] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Hengyang, Peoples R China.;[Yuan, Lin; Cheng, Dan] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha, Peoples R China.
通讯机构:
[He, Longwei] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Dept Pharm & Pharmacol, Canc Res Inst,Hengyang Med Sch,Affiliated Hosp 1, Hengyang, Peoples R China.
关键词:
surgical navigation;NIR-I;NIR-II;tumor;Fluorescence Imaging;Image-guided cancer surgeries
摘要:
Cancer is still one of the main causes of morbidity and death rate around the world, although diagnostic and therapeutic technologies are used to advance human disease treatment. Currently, surgical resection of solid tumors is the most effective and a prior remedial measure to treat cancer. Although medical treatment, technology, and science have advanced significantly, it is challenging to completely treat this lethal disease. Near-infrared (NIR) fluorescence, including the first near-infrared region (NIR-I, 650–900nm) and the second near-infrared region (NIR-II, 1,000–1,700nm), plays an important role in image-guided cancer surgeries due to its inherent advantages, such as great tissue penetration, minimal tissue absorption and emission light scattering, and low autofluorescence. By virtue of its high precision in identifying tumor tissue margins, there are growing number of NIR fluorescence-guided surgeries for various living animal models as well as patients in clinical therapy. Herein, this review introduces the basic construction and operation principles of fluorescence molecular imaging technology, and the representative application of NIR-I/II image-guided surgery in biomedical research studies are summarized. Ultimately, we discuss the present challenges and future perspectives in the field of fluorescence imaging for surgical navigation and also put forward our opinions on how to improve the efficiency of the surgical treatment. Copyright © 2021 Li, Cheng, He and Yuan.
语种:
英文
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多价环状模板法合成交联胶束和类环胶体
作者:
Zhang Miao;Peng Jinlei;Liu Ying;Liu Fangjun;Ma Wei;...
期刊:
高等学校化学学报 ,2021年42(11):3526-3536 ISSN:0251-0790
通讯作者:
Wei Hua
作者机构:
[Wei Hua; Zhang Miao; Liu Ying] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Wei Hua; Ma Wei; Zhang Miao; Peng Jinlei; Liu Fangjun] Lanzhou Univ, Key Lab Nonferrous Met Chem & Resources Utilizat, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China.
通讯机构:
[Wei Hua] U;[Wei Hua] L;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Dept Pharm & Pharmacol, Hengyang 421001, Peoples R China.;Lanzhou Univ, Key Lab Nonferrous Met Chem & Resources Utilizat, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China.
关键词:
交联胶束;类环胶体;多价环状模板
摘要:
通过点击偶联法,用二茂铁(Fc)修饰环状聚甲基丙烯酸羟乙酯[c-P(HEMA)50]的侧链羟基,得到多价环状聚合物模板c-P(HEMA-Fc)50,该模板可通过β-CD/Fc的主客体识别作用,在Fc位点有序偶联以亲水聚乙二醇(PEG)和硫辛酸(LA)功能化的β-环糊精(β-CD),形成具有明显核壳结构的超分子胶束[c-P(HEMA-Fc)50/β-CDPEG-LA].该超分子胶束可通过二硫苏糖醇(DTT)催化的分子内自交联(CL)形成交联的超分子胶束,作为交联β-CD-PEG-LA的环状胶体前驱体.与三臂星状聚合物模板相比,环状聚合物模板的优势在于环状多价结构具有更高的稳定性和空间位阻效应,以环状聚合物为模板制备的交联胶束和类环胶体的胶束前驱溶液的浓度可显著提高至1.0 mg/mL.
语种:
中文
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Fabrication of hypoxia-responsive and uperconversion nanoparticles-modified RBC micro-vehicles for oxygen delivery and chemotherapy enhancement
作者:
Wang, Peiyuan;Jiang, Suhua;Li, Yang;Luo, Qiang;Lin, Jinyan;...
期刊:
Biomaterials Science ,2020年8(16):4595-4602 ISSN:2047-4830
通讯作者:
Fan, Lingling;Zhu, Jun
作者机构:
[Jiang, Suhua; Luo, Qiang; Lin, Jinyan; Wang, Peiyuan; Li, Yang] Chinese Acad Sci, Fujian Inst Res Struct Matter, Key Lab Design & Assembly Funct Nanostruct, Fuzhou 350002, Peoples R China.;[Luo, Qiang; Fan, Lingling; Xu, Congjian; Wang, Peiyuan] Fudan Univ, Obstet & Gynecol Hosp, Shanghai 200011, Peoples R China.;[Jiang, Suhua; Luo, Qiang; Lin, Jinyan; Wang, Peiyuan; Li, Yang] Fujian Med Univ, Mengchao Hepatobiliary Hosp, United Innovat Mengchao Hepatobiliary Technol Key, Fuzhou 350025, Peoples R China.;[Jiang, Suhua; Lin, Jinyan; Wang, Peiyuan; Li, Yang] Chinese Acad Sci, Xiamen Inst Rare Earth Mat, Dept Translat Med, Xiamen 361024, Peoples R China.;[Hu, Lidan] Univ South China, Dept Biochem & Mol Biol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
通讯机构:
[Fan, Lingling] F;[Zhu, Jun] T;Fudan Univ, Obstet & Gynecol Hosp, Shanghai 200011, Peoples R China.;Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Oncol, Shanghai, Peoples R China.
摘要:
Solid tumor cells in hypoxic regions resist chemotherapy treatment with conventional antitumor drugs (such as paclitaxel, PTX) because the inadequate O2 attenuates the intracellular generation of reactive oxygen species (ROS) and upregulates multidrug resistance protein expression. Hyperbaric O2 therapy concentrates on improving O2 delivery to the hypoxic tumor area, thereby enhancing the sensitivity of cancer cells to chemotherapy drugs. However, the implementation of this therapy often elicits immune response or potentiates toxicity of the drugs toward normal cells. In this work, we successfully fabricated RBC-based micro-vehicles for precise hypoxia-activated O2 delivery under the 980 nm laser irradiation. Interestingly, the subsequent chemotherapy of PTX for ovarian tumors was significantly enhanced owing to the alleviation of hypoxia tumor microenvironment. Meanwhile, the RBC-based micro-vehicles have low side tissue effects, superior biocompatibility, and ultra-low immune response. Overall, the RBC-based drug delivery system holds a fascinating perspective towards O2 delivery for chemotherapy enhancement in other clinical solid malignancies. This journal is © The Royal Society of Chemistry.
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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Quantitatively Fine-Tuning the Physicochemical and Biological Properties of Peptidic Polymers through Monodisperse PEGylation
作者:
Wang, Xuemeng;Li, Yu;Wu, Tingjuan;Yang, Zhigang;Zheng, Xing;...
期刊:
Biomacromolecules ,2020年21(2):725-731 ISSN:1525-7797
通讯作者:
Zhou, Xin;Jiang, Zhong-Xing
作者机构:
[Jiang, Zhong-Xing; Wang, Xuemeng; Yang, Zhigang] Wuhan Univ, Wuhan, Peoples R China.;[Li, Yu; Zhou, Xin; Chen, Shizhen] Chinese Acad Sci, Wuhan, Peoples R China.;[Wu, Tingjuan; Zheng, Xing] Univ South China, Hengyang, Peoples R China.
通讯机构:
[Zhou, Xin] C;[Jiang, Zhong-Xing] W;Chinese Acad Sci, Wuhan, Peoples R China.;Wuhan Univ, Wuhan, Peoples R China.
摘要:
In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it is challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation strategies, including backbone PEGylation, side-chain PEGylation, and highly branched PEGylation, have been developed. In a comparative fashion, the impact of PEGylation strategies and monodisperse PEG sizes on the physicochemical and biological properties, including lipophilicity, thermosensitivity, biocompatibility, plasma stability, and drug delivery capability, of peptidic polymers has been quantitatively studied. It was found that the physicochemical and biological properties of PEGylated peptidic polymers can be quantitatively fine-tuned and accurately predicted through these monodisperse PEGylation strategies. After the comparative study, a side-chain monodisperse PEGylated peptidic polymer was chosen as fluorine-19 magnetic resonance and fluorescence dual-imaging traceable drug delivery vehicle. Our study may not only promote the transformation of PEGylation from an empirical technology to a quantitative science but also shed light on the rational design of PEGylated biomaterials and pharmaceutics.
语种:
英文
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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
语种:
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 19F magnetic resonance imaging (19F 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 19F 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” 19F 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. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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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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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;black phosphorus;surface modification;bioevaluation
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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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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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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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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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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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:
pH-sensitive;Prodrug;Co-delivery;Tumor therapy;Low toxicity
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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