Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy  

作　　者：Mengjuan Sun Muye Zhou Yifang Xiao Hailei Tang Jinhua Chen Ruitao Zhang Chunjiayu Li Qi Ya Qian Chen Jiasheng Tu Qiyue Wang Chunmeng Sun 

机构地区：[1]NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients,China Pharmaceutical University,Nanjing 210009,China [2]State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 211198,China [3]Department of Pharmaceutics,School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China [4]Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China [5]School of Pharmaceutical Science,Nanjing Tech University,Nanjing 211816,China

出　　处：《Chinese Chemical Letters》2024年第7期377-382,共6页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81972894,22278442,82273882)。

摘　　要：Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral efficacy.Particles with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid pressure.To address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this study.The micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),encapsulated.The net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of micelles.DE-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral pH.Results indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse model.Collectively,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.

关 键 词：Polyion complex micelle Size-switchable Revisable size-change pH response Antiangiogenic cancer 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R730.5[医药卫生—肿瘤]