title: Polypeptide cationic micelles mediated co-delivery of docetaxel and siRNA for synergistic tumor therapy.
abstract: Combination of two or more therapeutic strategies with different mechanisms can cooperatively impede tumor growth. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a single nanoparticle (NP) provides a rational strategy for combined cancer therapy. Here, we prepared polypeptide micelle nanoparticles (NPs) of a triblock copolymer poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) to systemically codeliver docetaxel (DTX) and siRNA-Bcl-2 for an effective drug/gene vector. The hydrophobic PLLeu core entrapped with anticancer drugs, while the PLL polypeptide cationic backbone allowed for electrostatic interaction with the negatively charged siRNA. The resulting micelle NP exhibited very stable, good biocompatible and excellent passive targeted properties. The micelle complexes with siRNA-Bcl-2 effectively knocked down the expression of Bcl-2 mRNA and protein. Moreover, the co-delivery system of DTX and siRNA-Bcl-2 (DTX-siRNA-NPs) obviously down-regulation of the anti-apoptotic Bcl-2 gene and enhanced antitumor activity with a smaller dose of DTX, resulting the significantly inhibited tumor growth of MCF-7 xenograft murine model as compared to the individual siRNA and only DTX treatments. Our results demonstrated well-defined PEG-PLL-PLLeu polypeptide cationic micelles with the excellent synergistic effect of DTX and siRNA-Bcl-2 in combined cancer therapy.
authors: CAS Key Lab of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors: Cuifang
authors: C
authors: Zheng
authors: Mingbin
authors: M
authors: Zheng
authors: Ping
authors: P
authors: Gong
authors: Jizhe
authors: J
authors: Deng
authors: Huqiang
authors: H
authors: Yi
authors: Pengfei
authors: P
authors: Zhang
authors: Yijuan
authors: Y
authors: Zhang
authors: Peng
authors: P
authors: Liu
authors: Yifan
authors: Y
authors: Ma
authors: Lintao
authors: L
authors: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002412:Cations; D049109:Cell Proliferation / Q000187:drug effects; D003102:Colloids; D000077143:Docetaxel; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D014018:Tissue Distribution / Q000187:drug effects; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D003102:Colloids; D008823:Micelles; D010455:Peptides; D011108:Polymers; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel