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. (C) 2016 Elsevier B.V. All rights reserved.
[1]Second Mil Med Univ, Changhai Hosp, Dept Pharmaceut, Shanghai 200433, Peoples R China.
[2]Chinese Peoples Liberat Army Gen Hosp, Pharm Care Ctr, Beijing 100853, Peoples R China.
[3]Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Pharmaceut, Shanghai 200080, Peoples R China.
[4]Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western, Dept Pharm, Shanghai 200437, Peoples R China.
[5]Hebei North Univ, Dept Pharmacol, Zhangjiakou 075000, Hebei, Peoples R China.
[6]Acad Mil Med Sci, Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China.
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