编程组装/释放多功能 miRNA 纳米药物治疗前列腺癌。

Programing Assembling/Releasing Multifunctional miRNA Nanomedicine to Treat Prostate Cancer.

机构信息

Central Laboratory, Ren Ji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200127 , China.

State Key Laboratory of Oncogenes and Related Genes , Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032 , China.

出版信息

ACS Appl Mater Interfaces. 2020 Feb 26;12(8):9032-9040. doi: 10.1021/acsami.9b21707. Epub 2020 Feb 7.

DOI:10.1021/acsami.9b21707

PMID:31986004

Abstract

MicroRNAs (miRNAs) therapy has shown to have great promise for the treatment of androgen-independent prostate cancer (AIPC) due to the low efficiency of hormonal therapy. However, instability of RNA and inefficiency of RNA therapy limit the use of miRNAs in the treatment of AIPC. Here, we report a pH/ATP-activated nanocomplexes for increasing cytosolic delivery of miR146a which can effectively inhibit the expression of epidermal growth factor receptor (EGFR) in AIPC. The nanocomplexes show identical suppressing effect in invasion, colony formation, migration ability, and growth of DU145 cells compared with Lipofectamine 2000 (lipo). But for in vivo experiments, the nanocomplexes vigorously suppress the growth of tumor volumes comparing to lipo group after five weeks' treatment. These results demonstrate the potential of the pH/ATP-activated nanocarriers for AIPC gene therapy.

摘要

微小 RNA（miRNAs）疗法由于激素治疗效率低下，显示出在治疗雄激素非依赖性前列腺癌（AIPC）方面具有巨大的应用前景。然而，RNA 的不稳定性和 RNA 治疗的低效率限制了 miRNAs 在 AIPC 治疗中的应用。在这里，我们报告了一种 pH/ATP 激活的纳米复合物，用于增加 miR146a 的细胞质递送，该 miR146a 可以有效抑制 AIPC 中表皮生长因子受体（EGFR）的表达。与 Lipofectamine 2000（脂质体）相比，纳米复合物在 DU145 细胞的侵袭、集落形成、迁移能力和生长方面显示出相同的抑制作用。但是对于体内实验，在五周的治疗后，纳米复合物组比脂质体组强烈抑制肿瘤体积的生长。这些结果表明 pH/ATP 激活的纳米载体在 AIPC 基因治疗方面具有潜力。