title: Synergistic effect of reduced polypeptide micelle for co-delivery of doxorubicin and TRAIL against drug-resistance in breast cancer.
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.
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chuling
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Gu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Tai
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chunai
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage*; D008063:Thioctic Acid / Q000737:chemistry; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D008823:Micelles; D010455:Peptides; D011108:Polymers; D053221:TNF-Related Apoptosis-Inducing Ligand; C015462:polyarginine; D008063:Thioctic Acid; D004317:Doxorubicin
keywords: cancer therapy; drug resistance; lipoic acid; polyarginine; reduction-sensitive