Development of octreotide-conjugated polymeric prodrug of bufalin for targeted delivery to somatostatin receptor 2 overexpressing breast cancer in vitro and in vivo.
Development of octreotide-conjugated polymeric prodrug of bufalin for targeted delivery to somatostatin receptor 2 overexpressing breast cancer in vitro and in vivo.
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DOI：
10.2147/ijn.s100404
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发表时间：
2016
影响因子：
8
通讯作者：
Yuan Y
中科院分区：
文献类型：
--
作者：
Liu T;Jia T;Yuan X;Liu C;Sun J;Ni Z;Xu J;Wang X;Yuan Y
开发高分子前药是克服小分子抗癌药物固有缺陷、提高其抗癌性能的最有前途的策略之一。在目前的工作中，我们制造了一种新的奥曲肽（Oct）修饰的酯酶敏感的肿瘤靶向蟾蜍灵（BUF）的聚合物前药，并探讨其对生长抑素受体2过表达的乳腺癌的抗癌性能。所获得的BUF的肿瘤靶向聚合物前药P（寡[乙二醇]单甲醚甲基丙烯酸酯[OEGMA]-co-BUF-co-Oct）在酯酶存在下显示出纳米尺寸和控制药物释放特征。体外实验表明，P（OEGMA-co-BUF-co-Oct）与游离BUF相比，具有更强的细胞毒性、细胞摄取和细胞凋亡。体内实验进一步揭示了P（OEGMA-co-BUF-co-Oct）在肿瘤组织中的药物积累和增强的抗癌性能。总之，这项研究表明，BUF的聚合物前体药物对治疗生长抑素受体2过表达的乳腺癌具有很好的潜力。
Development of polymeric prodrugs of small molecular anticancer drugs has become one of the most promising strategies to overcome the intrinsic shortcomings of small molecular anticancer drugs and improve their anticancer performance. In the current work, we fabricated a novel octreotide (Oct)-modified esterase-sensitive tumor-targeting polymeric prodrug of bufalin (BUF) and explored its anticancer performance against somatostatin receptor 2 overexpressing breast cancer. The obtained tumor-targeting polymeric prodrug of BUF, P(oligo[ethylene glycol] monomethyl ether methacrylate [OEGMA]-co-BUF-co-Oct), showed a nanosize dimension and controlled drug release features in the presence of esterase. It was demonstrated by in vitro experiment that P(OEGMA-co-BUF-co-Oct) showed enhanced cytotoxicity, cellular uptake, and apoptosis in comparison with those of free BUF. In vivo experiment further revealed the improved accumulation of drugs in tumor tissues and enhanced anticancer performance of P(OEGMA-co-BUF-co-Oct). Taken together, this study indicated that polymeric prodrug of BUF holds promising potential toward the treatment of somatostatin receptor 2 overexpressing breast cancer.