title: A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery.
abstract: A amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mPEG-PLGA-b-PLL) was synthesized. The chemical structure of this copolymer and its precursors was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), (1)H Nuclear Magnetic Resonance ((1)H NMR) and Gel Permeation Chromatography (GPC). The copolymer was used to prepare nanoparticles (NPs) that were then loaded with either the anti-cancer drug adriamycin or small interfering RNA-negative (siRNA) using a double emulsion method. MTT assays used to study the in vitro cytotoxicity of mPEG-PLGA-b-PLL NPs showed that these particles were not toxic in huh-7 hepatic carcinoma cells. Confocal laser scanning microscopy (CLSM) and flow cytometer analysis results demonstrated efficient mPEG-PLGA-b-PLL NPs-mediated delivery of both adriamycin and siRNA into the cells. In vivo the targeting delivery of adriamycin or siRNA mediated by mPEG-PLGA-b-PLL NPs in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. The targeting delivery results and froze section analysis confirmed that drug or siRNA is deliver to tumor more efficiently by mPEG-PLGA-b-PLL NPs than free drug or Lipofectamine™2000. The high efficiency delivery of mPEG-PLGA-b-PLL NPs mainly due to the enhancement of cellular uptake. These results imply that mPEG-PLGA-b-PLL NPs have a great potential to be used as an effective carriers for adriamycin or siRNA.
authors.affiliation: Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, PR China.
authors.forename: Peifeng
authors.initials: P
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhu
authors.forename: Yourong
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D008239:Lysine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000633:toxicity / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D058105:Polymerization / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000588:Amines; D004337:Drug Carriers; D011091:Polyesters; D034741:RNA, Small Interfering; C574222:monomethoxy (polyethylene glycol)-poly(lactide-co-glycolide)-poly(lysine); D011107:Polylysine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D008239:Lysine