Synergistic effect of reduced polypeptide micelle for co-delivery of doxorubicin and TRAIL against drug-resistance in breast cancer
PDF | HTML | How to cite
Metrics: PDF 1478 views | HTML 2044 views | ?
Chuling Hu1,*, Fenfen Gu1,*, Zongguang Tai1,*, Chong Yao1, Chunai Gong1, Qingming Xia1, Yuan Gao1, Shen Gao1
1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*These authors contributed equally to this work
Shen Gao, email: [email protected]
Yuan Gao, email: [email protected]
Keywords: polyarginine, lipoic acid, reduction-sensitive, drug resistance, cancer therapy
Received: May 02, 2016 Accepted: August 13, 2016 Published: August 20, 2016
Cationic peptides as a non-viral gene vector have become a hotspot of research because of their high transfection efficcacy and safety. Based on our previous study, we synthesized a cationic reduction-responsive vector based on disulfide cross-linked L-arginine, L-histidine and lipoic acid (LHRss) as the co-carrier of both doxorubicin (DOX) and the necrosis factor-related apoptosis-inducing ligand (pTRAIL). The LHRss/DOX/TRAIL construct has reduction-sensitive behavior and an enhanced endosomal escape ability to increase the cytotoxicity of DOX and the transfection efficiency. Further, the LHRss/DOX/TRAIL construct increased the accumulation of DOX and promoted the expression of pTRAIL, thus increasing cellular apoptosis by 83.7% in MCF-7/ADR cells. In addition, the in vivo biodistribution results showed that the LHRss/DOX/TRAIL construct could target tumors well. The in vivo anti-tumor effect study demonstrated that the LHRss/DOX/TRAIL construct inhibited tumor growth markedly, with a tumor inhibitory rate of 94.0%. The co-delivery system showed a significant synergistic anti-tumor effect. The LHRss/DOX/TRAIL construct may prove to be a promising co-delivery vector for the effective treatment of drug resistant breast cancer.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.