Zhejiang Key Laboratory of Smart BioMaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, China; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Zhejiang Key Laboratory of Smart BioMaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, China; Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
J Control Release. 2022 Feb;342:122-133. doi: 10.1016/j.jconrel.2022.01.002. Epub 2022 Jan 5.
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.
从传统中药中提取的天然三萜 Celastrol 对各种癌细胞表现出抗癌作用。然而，其较差的水溶性、较短的血浆半衰期和较高的全身毒性阻碍了其在体内的应用，需要一个稳定的药物传递系统来克服这些关键的缺陷。我们在这里提出了一种嵌段共聚物，聚（2-（N-氧化物-N，N-二甲基氨基）乙基甲基丙烯酸酯）-嵌段-聚（2-羟乙基甲基丙烯酸酯）（OPDMA-HEMA），作为 Celastrol 传递的载体。两亲聚合物-Celastrol 缀合物可以在水溶液中自组装成纳米颗粒。OPDMA 外壳赋予纳米颗粒更好的药代动力学和有效的线粒体靶向能力，并显著增强 Celastrol 诱导免疫原性细胞死亡的能力，这共同导致 Celastrol 在体内治疗效果的增强。这种靶向线粒体的聚合物-Celastrol 缀合物可能有望将 Celastrol 应用于癌症治疗。
