HPMA聚合物交联胶束的制备及抗乳腺癌活性

Preparation of HPMA copolymer cross-linked micelles and their anti-breast cancer activity

为增加抗肿瘤药物H1-S6A,F8A多肽的治疗效果,将其与具有细胞核靶向能力的全反式视黄酸结合,形成的结合物H1RA包裹至两亲性N-(2-羟丙基)甲基丙烯酰胺(N-(2-hydroxypropyl)methacrylamide,HPMA)聚合物所形成的交联胶束中。对该交联胶束的性质及MCF7人乳腺癌细胞和荷瘤裸鼠的抗肿瘤药效进行了考察。结果表明,该交联胶束粒径约为53nm,包载的药物在生理环境下释放缓慢,在模拟溶酶体的酸性环境中可迅速释放。较之H1RA具有更好的抑制MCF7肿瘤细胞生长作用,其IC50值仅为H1RA的17%。交联胶束对荷MCF7移植瘤的裸鼠也展现出更强的肿瘤抑制效果,其抑瘤率为H1RA的1.8倍。

To increase the therapeutic effect of the anti-tumor drug H1-S6 A,F8 Apeptide,it was combined with all-trans retinoic acid which has nuclear targeting ability.Then the conjugate H1 RA was encapsulated to cross-linked micelles formed by amphiphilic N-（2-hydroxypropyl）methacrylamide（HPMA）copolymer.The characters of the cross-linked micelles as well as their in vitro and in vivo anti MCF7 human breast cancer efficacy were investigated.The results show that the size of the crosslinked micelles is about 53 nm.The drug is released slowly under physiological environment,and can be released rapidly in the acidic environment which simulating lysosomes.For MCF7 human breast cancer cells,cross-linked micelles have a better growth inhibitory effect than H1 RA,and their IC50 value is only 17% of H1 RA.Cross-linked micelles also show better tumor inhibition in nude mice bearing MCF7 xenografts with a 1.8-fold inhibition rate of H1 RA.