Mitochondria-targeted polymer-celastrol conjugate with enhanced anticancer efficacy.

Yu Geng, Jiajia Xiang, Shiqun Shao, Jianbin Tang, Youqing Shen

Journal of controlled release : official journal of the Controlled Release Society 2022 Feb

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Celastrol, a natural triterpene extracted from traditional Chinese medicine, shows anticancer effects on various cancer cells. However, its poor water-solubility, short plasma half-life, and high systemic toxicity impede its applications in vivo, necessitating a stable drug delivery system to overcome these critical drawbacks. We present here a block copolymer, poly(2-(N-oxide-N,N-dimethylamino)ethyl methacrylate)-block-poly(2-hydroxyethyl methacrylate) (OPDMA-HEMA), as the carrier for celastrol delivery. The amphiphilic polymer-celastrol conjugate can self-assemble into nanoparticles in aqueous solutions. The OPDMA outer shell confers the nanoparticles with improved pharmacokinetics and efficient mitochondria targeting capacity, and profoundly potentiates celastrol's induction of immunogenic cell death, which collectively contribute to the enhanced therapeutic effects of celastrol in vivo. This mitochondria-targeted polymer-celastrol conjugate may promise the applications of celastrol in cancer treatment. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Yu Geng, Jiajia Xiang, Shiqun Shao, Jianbin Tang, Youqing Shen. Mitochondria-targeted polymer-celastrol conjugate with enhanced anticancer efficacy. Journal of controlled release : official journal of the Controlled Release Society. 2022 Feb;342:122-133