Oncotarget

Research Papers:

Synergistic effect of reduced polypeptide micelle for co-delivery of doxorubicin and TRAIL against drug-resistance in breast cancer

Chuling Hu, Fenfen Gu, Zongguang Tai, Chong Yao, Chunai Gong, Qingming Xia, Yuan Gao and Shen Gao _

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Oncotarget. 2016; 7:61832-61844. https://doi.org/10.18632/oncotarget.11451

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Abstract

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

Correspondence to:

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

ABSTRACT

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.


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