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Nuclear-targeting TAT-PEG-Asp(8)-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer

文献类型：期刊论文

作者Pan, Zhen-zhen1,2; Wang, Hui-yuan2; Zhang, Meng2; Lin, Ting-ting2; Zhang, Wen-yuan2; Zhao, Peng-fei2; Tang, Yi-si1,2; Xiong, Yong3; Zeng, Yuan-er1; Huang, Yong-zhuo2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2016-08
卷号37期号:8页码:1110-1120
关键词doxorubicin multidrug resistance cell-penetrating peptide poly(aspartic acid) intranuclear delivery nanoparticles human colon cancer HCT8/ADR cells
ISSN号1671-4083
DOI10.1038/aps.2016.48
文献子类Article
英文摘要Aim: Drug efflux-associated multidrug resistance (MDR) is a main obstacle to effective cancer chemotherapy. Large molecule drugs are not the substrates of P-glycoprotein, and can circumvent drug efflux and be retained inside cells. In this article we report a polymer-drug conjugate nanoparticulate system that can overcome MDR based on size-related exclusion effect. Methods: Doxorubicin was coupled with the triblock polymeric material cell-penetrating TAT-PEG-poly(aspartic acid). The amphiphilic macromolecules (termed TAT-PEG-Asp(8)-Dox) could self-assemble into nanoparticles (NPs) in water. The antitumor activity was evaluated in drug-resistant human colon cancer HCT8/ADR cells in vitro and in nude mice bearing HCT8/ADR tumor. Results: The self-assembling TAT-PEG-Asp(8)-Dox NPs were approximately 150 nm with a narrow particle size distribution, which not only increased the cellular uptake efficiency, but also bypassed P-glycoprotein-mediated drug efflux and improved the intracellular drug retention, thus yielding an enhanced efficacy for killing drug-resistant HCT8/ADR colon cancer cells in vitro. Importantly, the TAT-PEGA-sp(8)-Dox NPs enhanced the intranuclear disposition of drugs for grater inhibition of DNA/RNA biosynthesis. In nude mice bearing xenografted HCT8/ADR colon cancers, intravenous or peritumoral injection of TAT-PEG-Asp(8)-Dox NPs for 22 d effectively inhibited tumor growth. Conclusion: TAT-PEG-Asp(8)-Dox NPs can increase cellular drug uptake and intranuclear drug delivery and retain effective drug accumulation inside the cells, thus exhibiting enhanced anticancer activity toward the drug-resistant human colon cancer HCT8/ADR cells.
WOS关键词MESOPOROUS SILICA NANOPARTICLES ; CELL PENETRATING PEPTIDES ; MULTIDRUG-RESISTANCE ; P-GLYCOPROTEIN ; PLGA NANOPARTICLES ; COLORECTAL-CANCER ; BREAST-CANCER ; DELIVERY ; CHEMOTHERAPY ; INHIBITION
资助项目973 Program, China[2014CB931900] ; 973 Program, China[2013CB932503] ; National Natural Science Foundation of China[81172996] ; National Natural Science Foundation of China[81373357] ; National Natural Science Foundation of China[81422048] ; National Natural Science Foundation of China[81402883] ; National Natural Science Foundation of China[81521005]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5766621
WOS记录号WOS:000380927200011
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/275940]  
专题药物制剂研究中心
通讯作者Zeng, Yuan-er; Huang, Yong-zhuo
作者单位1.Guangzhou Univ Chinese Med, Sch Chinese Mat Med, Guangzhou 510405, Guangdong, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
3.Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China
推荐引用方式
GB/T 7714		 Pan, Zhen-zhen,Wang, Hui-yuan,Zhang, Meng,et al. Nuclear-targeting TAT-PEG-Asp(8)-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer[J]. ACTA PHARMACOLOGICA SINICA,2016,37(8):1110-1120.
APA Pan, Zhen-zhen.,Wang, Hui-yuan.,Zhang, Meng.,Lin, Ting-ting.,Zhang, Wen-yuan.,...&Huang, Yong-zhuo.(2016).Nuclear-targeting TAT-PEG-Asp(8)-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer.ACTA PHARMACOLOGICA SINICA,37(8),1110-1120.
MLA Pan, Zhen-zhen,et al."Nuclear-targeting TAT-PEG-Asp(8)-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer".ACTA PHARMACOLOGICA SINICA 37.8(2016):1110-1120.

入库方式： OAI收割

来源：上海药物研究所

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