title: Smac therapeutic Peptide nanoparticles inducing apoptosis of cancer cells for combination chemotherapy with Doxorubicin.
abstract: Smac-conjugated nanoparticle (Smac-NP) was designed to induce the apoptosis of cancer cells and as a drug carrier for combination therapy. It contained three parts, a SmacN7 peptide which could induce apoptosis of cancer cells by interacting with XIAPs, the cell penetrating domain rich in arginine, and four hydrophobic tails for self-assembled Smac-NP. We demonstrated that Smac-NPs exerted an antitumor effect in breast cancer cell MDA-MB-231 and nonsmall lung cancer (NSCLC) cell H460, which efficiently inhibited cancer cells proliferation without influencing normal liver cell lines LO2. Smac-NPs also significantly induced apoptosis of MDA-MB-231 and H460 cells through activating pro-caspase-3, down-regulating the expression of antiapoptotic protein Bcl-2 and up-regulating the pro-apoptotic protein Bax. Furthermore, Smac-NPs could be explored as a drug delivery system to load hydrophobic drug such as DOX for combination therapy. The DOX-loaded nanoparticles (DOX-Smac-NPs) exhibited higher cellular uptake efficiency and antitumor effect. Our work provided a new insight into therapeutic peptides integrated with drug simultaneously in one system for cancer combination treatment.
authors: †School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
authors: Mingxing
authors: M
authors: Li
authors: ‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Peng
authors: P
authors: Liu
authors: ‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Guanhui
authors: G
authors: Gao
authors: ‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Jizhe
authors: J
authors: Deng
authors: ‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Zhengyin
authors: Z
authors: Pan
authors: †School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
authors: Xu
authors: X
authors: Wu
authors: ‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Gaofeng
authors: G
authors: Xie
authors: §Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Shanghai Jiao Tong University, Shanghai 200240, China.
authors: Caixia
authors: C
authors: Yue
authors: †School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
authors: Chi Hin
authors: CH
authors: Cho
authors: ‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Yifan
authors: Y
authors: Ma
authors: ‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Lintao
authors: L
authors: Cai
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D009842:Oligopeptides / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D053769:Nanocapsules; D009842:Oligopeptides; C532637:SMAC peptide; D004317:Doxorubicin
keywords: Smac; combination therapy; drug delivery; therapeutic peptides