Reducible self-assembling cationic polypeptide-based micelles mediate co-delivery of doxorubicin and microRNA-34a for androgen-independent prostate cancer therapy

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• 作者：Chong Yao^a ; ^b ; ¹ ; Jiyong Liu^a ; ¹ ; Xin Wu^c ; ¹ ; Zongguang Tai^a ; Yuan Gao^a ; Quangang Zhu^d ; Jiafei Li^e ; Lijuan Zhang^a ; Chuling Hu^a ; Fenfen Gu^a ; Jing Gao^f ; ^{gjsmmu@126.com" class="auth_mail" title="E-mail the corresponding author} ; Shen Gao^a ; ^{liullk@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Polypeptide micelle ; Doxorubicin ; miR-34a ; Co-delivery ; Synergistic effect
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 June 2016
• 年：2016
• 卷：232
• 期：Complete
• 页码：203-214
• 全文大小：2744 K

文摘

The co-delivery of chemotherapeutic drugs and microRNAs (miR) represents a promising strategy for tumor therapy due to the synergistic effect achieved. In the present study, hydrophobic doxorubicin (DOX) and negatively charged miR-34a were simultaneously delivered via a reducible self-assembling disulfide cross-linked stearyl-peptide-based micellar system (SHRss) using poly(l-arginine)-poly(l-histidine)-stearoyl as the copolymer building unit. The nanoscale SHRss micelles exhibited a low critical micelle concentration (CMC) with positive surface charge. In addition, the present micellar system facilitated the escape of miR-34a from the endosome and release of DOX into the cell nucleus, leading to the downregulation of silent information regulator 1 (SIRT1) expression and inhibition of DU145 and PC3 androgen-independent prostate cancer cell proliferation. In addition, DOX and miR-34a, delivered by SHRss micelles, passively targeted tumor tissue. Furthermore, a synergistic anti-proliferative effect was observed compared with DOX or miR-34a treatment alone in vivo. Our results demonstrate that the SHRss micelles developed in the present study represent a promising approach for combined delivery of gene agents and hydrophobic chemotherapeutic drugs in cancer therapy.