Journal
JOURNAL OF CONTROLLED RELEASE
Volume 232, Issue -, Pages 203-214Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2016.04.034
Keywords
Polypeptide micelle; Doxorubicin; miR-34a; Co-delivery; Synergistic effect
Funding
- NSFC [81372762, 81272819, 81302212, 81172514, 81573613]
- National Science and Technology Major Projects for Major New Drugs Innovation and Development [2013ZX09J13109-04B]
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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.
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