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

Abstract

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.

• Authors: Chong Yao, Jiyong Liu, Xin Wu, Zongguang Tai, Yuan Gao, Quangang Zhu, Jiafei Li, Lijuan Zhang, Chuling Hu, Fenfen Gu, Jing Gao, Shen Gao
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 232 Pg. 203-14 (06 28 2016) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 27126903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• MIRN34 microRNA, human
• Micelles
• MicroRNAs
• Peptides
• RNA, Messenger
• Doxorubicin
• SIRT1 protein, human
• Sirtuin 1

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Doxorubicin (administration & dosage)
• Drug Delivery Systems
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• MicroRNAs (administration & dosage)
• Peptides (administration & dosage)
• Prostatic Neoplasms (genetics, metabolism, therapy)
• RNA, Messenger (metabolism)
• Sirtuin 1 (genetics, metabolism)