Citation: Mengjuan Sun, Muye Zhou, Yifang Xiao, Hailei Tang, Jinhua Chen, Ruitao Zhang, Chunjiayu Li, Qi Ya, Qian Chen, Jiasheng Tu, Qiyue Wang, Chunmeng Sun. Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy[J]. Chinese Chemical Letters, ;2024, 35(7): 109110. doi: 10.1016/j.cclet.2023.109110 shu

Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

Mengjuan Sun ^{a, b, c, 1} ,
Muye Zhou ^{a, b, c, 1} ,
Yifang Xiao ^{a, b, c} ,
Hailei Tang ^{a, b, c} ,
Jinhua Chen ^{a, b, c} ,
Ruitao Zhang ^{a, b, c} ,
Chunjiayu Li ^{a, b, c} ,
Qi Ya ^{a, b, c} ,
Qian Chen ^{a, d} ,
Jiasheng Tu ^{a, b, c, *,} ,
Qiyue Wang ^{e, *,} ,
Chunmeng Sun ^{a, b, c, *,}

a.
NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China
b.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
c.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
d.
Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
e.
School of Pharmaceutical Science, Nanjing Tech University, Nanjing 211816, China

jiashengtu@cpu.edu.cn

qiyue.wang@njtech.edu.cn

suncmpharm@cpu.edu.cn

Received Date: 28 July 2023
Revised Date: 13 September 2023
Accepted Date: 14 September 2023
Available Online: 16 September 2023

Figures(4)

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 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 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 size-switchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.
- Polyion complex micelle,
- Size-switchable,
- Revisable size-change,
- pH response,
- Antiangiogenic cancer
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