One-Step Microfluidic Synthesis of Nanocomplex with Tunable Rigidity and Acid-Switchable Surface Charge for Overcoming Drug Resistance

doi:10.1002/smll.201603109

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	One-Step Microfluidic Synthesis of Nanocomplex with Tunable Rigidity and Acid-Switchable Surface Charge for Overcoming Drug Resistance
	Feng, Qiang 1,2,3; Liu, Jianping 4,5; Li, Xuanyu 1,2,3; Chen, Qinghua 2,3; Sun, Jiashu 1,2,3; Shi, Xinghua 1,6; Ding, Baoquan 1,6; Yu, Haijun4,5 ; Li, Yaping4,5 ; Jiang, Xingyu 1,2,3
刊名	SMALL
	2017-03-07
卷号	13 期号:9
ISSN号	1613-6810
DOI	10.1002/smll.201603109
文献子类	Article
英文摘要	Multidrug resistance (MDR), is the key reason accounting for the failure of cancer chemotherapy, remains a dramatic challenge for cancer therapy. In this study, the one- step microfluidic fabrication of a rigid pH-sensitive micellar nanocomplex (RPN) with tunable rigidity and acid-switchable surface charge for overcoming MDR by enhancing cellular uptake and lysosome escape is demonstrated. The RPN is composed of a poly(lactic-co-glycolic acid) (PLGA) core and a pH-sensitive copolymer shell, which is of neutral surface charge during blood circulation. Upon internalization of RPN by cancer cells, the pH-responsive shell dissociates inside the acidic lysosomes, while the rigid and positively charged PLGA core improves the lysosomal escape. The cellular uptake and nuclear uptake of doxorubicin (Dox) from Dox-loaded RPN are 1.6 and 2.4 times higher than that from Dox-loaded pH- sensitive micelles (PM) using a Dox-resistant cancer model (MCF-7/ADR, re-designated NCI/ADR- RES) in vitro. Dox- loaded RPN significantly enhances the therapeutic efficacy (92% inhibition of tumor growth) against MCF-7/ADR xenograft tumor in mice, while Dox- loaded PM only inhibits the tumor growth by 36%. RPN avoids the use of complicated synthesis procedure of nanoparticle and the necessary to integrate multiple components, which can facilitate the clinical translation of this novel nanostructure.
资助项目	MOST[2013AA032204] ; NSFC[21475028] ; NSFC[21622503] ; NSFC[31622025] ; NSFC[81361140345] ; Youth Innovation Promotion Association CAS[00000000]
WOS关键词	TARGETED SIRNA DELIVERY ; COARSE-GRAINED MODEL ; MULTIDRUG-RESISTANCE ; CELLULAR UPTAKE ; P-GLYCOPROTEIN ; CANCER-THERAPY ; BREAST-CANCER ; TUMOR ; NANOPARTICLES ; CELLS
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000397606100013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272746]
专题	药物制剂研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Sun, Jiashu; Yu, Haijun; Jiang, Xingyu
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 2.Natl Ctr NanoSci & Technol, Beijing Engn Res Ctr BioNanotechnol, 11 Beiyitiao, Beijing 100190, Peoples R China; 3.Natl Ctr NanoSci & Technol, CAS Key Lab Biol Effects Nanomat & Nanosafety, CAS Ctr Excellence Nanosci, 11 Beiyitiao, Beijing 100190, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China; 6.Natl Ctr Nanosci & Technol, CAS Key Lab Nanosyst & Hierarch Fabricat, CAS Ctr Excellence Nanosci, 11 Beiyitiao, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Feng, Qiang,Liu, Jianping,Li, Xuanyu,et al. One-Step Microfluidic Synthesis of Nanocomplex with Tunable Rigidity and Acid-Switchable Surface Charge for Overcoming Drug Resistance[J]. SMALL,2017,13(9).
APA	Feng, Qiang.,Liu, Jianping.,Li, Xuanyu.,Chen, Qinghua.,Sun, Jiashu.,...&Jiang, Xingyu.(2017).One-Step Microfluidic Synthesis of Nanocomplex with Tunable Rigidity and Acid-Switchable Surface Charge for Overcoming Drug Resistance.SMALL,13(9).
MLA	Feng, Qiang,et al."One-Step Microfluidic Synthesis of Nanocomplex with Tunable Rigidity and Acid-Switchable Surface Charge for Overcoming Drug Resistance".SMALL 13.9(2017).