首页|Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

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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 par-ticles are easily removed from tumor tissues due to the high tumor interstitial fluid pressure.To ad-dress these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly size-switchable 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 opti-mal 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 size-switchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.

Polyion complex micelleSize-switchableRevisable size-changepH responseAntiangiogenic cancer

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

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NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients,China Pharmaceutical University,Nanjing 210009,China

State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 211198,China

Department of Pharmaceutics,School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China

Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China

School of Pharmaceutical Science,Nanjing Tech University,Nanjing 211816,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China

819728942227844282273882

2024

10.1016/j.cclet.2023.109110

中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
年,卷(期)：2024.35(7)