α-Conotoxin ImI-modified polymeric micelles as potential nanocarriers for targeted docetaxel delivery to α7-nAChR overexpressed non-small cell lung cancer

Drug Delivery

Xin Ni¹  Xiaoyan Zhang¹  Xiaoling Wang¹  Dong Mei¹  Libo Zhao¹  Zhiying Yu²  Binlong Chen³  Qiang Zhang³ 

[1] Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, PR China;Department of Pharmacy, Peking University People’s Hospital, Beijing, PR Chin;State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, PR China;

关键词: α-Conotoxin ImI;    α7-nAChR;    non-small cell lung cancer (NSCLC);    PEG-DSPE micelles;    targeted delivery;   

DOI  :  10.1080/10717544.2018.1436097

来源: publisher

【 摘 要 】

A micelle system modified with α-Conotoxin ImI (ImI), a potently antagonist for alpha7 nicotinic acetylcholine receptor (α7-nAChR) previously utilized for targeting breast cancer, was constructed. Its targeting efficiency and cytotoxicity against non-small cell lung cancer (NSCLC) highly expressing α7-nAChR was investigated. A549, a non-small cell lung cancer cell line, was selected as the cell model. The cellular uptake study showed that the optimal modification ratio of ImI on micelle surface was 5% and ImI-modification increased intracellular delivery efficiency to A549 cells via receptor-mediated endocytosis. Intracellular Ca2+ transient assay demonstrated that ImI modification led to enhanced molecular interaction between nanocarriers and A549 cells. The in vivo near-infrared fluorescence imaging further revealed that ImI-modified micelles could facilitate the drug accumulation in tumor sites compared with non-modified micelles via α7-nAChR mediation. Moreover, docetaxel (DTX) was loaded in ImI-modified nanomedicines to evaluate its in vitro cytotoxicity. As a result, DTX-loaded ImI-PMs exhibited greater anti-proliferation effect on A549 cells compared with non-modified micelles. Generally, our study proved that ImI-modified micelles had targeting ability to NSCLC in addition to breast cancer and it may provide a promising strategy to deliver drugs to NSCLC overexpressing α7-nAChR.

【 授权许可】

CC BY