Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy
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 p...
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Veröffentlicht in: | Chinese chemical letters 2024-07, Vol.35 (7), p.109110, Article 109110 |
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Sprache: | eng |
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Zusammenfassung: | 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.
An intelligent core-crosslinked polyion complex micelle (cPCM) with a reversibly size-switchable feature was engineered to resolve the contradiction between penetration and retention of nanoparticles at tumor sites.
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ISSN: | 1001-8417 1878-5964 |
DOI: | 10.1016/j.cclet.2023.109110 |