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

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.

Journal of controlled release : official journal of the Controlled Release Society. 2016 Apr 25 [Epub ahead of print]

Chong Yao, Jiyong Liu, Xin Wu, Zongguang Tai, Yuan Gao, Quangang Zhu, Jiafei Li, Lijuan Zhang, Chuling Hu, Fenfen Gu, Jing Gao, Shen Gao

Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China., Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Pharmacy, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China., Department of pharmacology, Hebei North University, Hebei 075000, China., Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China., Institute of pharmacology & toxicology of Academy of Military Medical Sciences, Beijing 100850, China. Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. 

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