title: Core-shell nanoparticles based on pullulan and poly(β-amino) ester for hepatoma-targeted codelivery of gene and chemotherapy agent.
abstract: This study designs a novel nanoparticle system with core-shell structure based on pullulan and poly(β-amino) ester (PBAE) for the hepatoma-targeted codelivery of gene and chemotherapy agent. Plasmid DNA expressing green fluorescent protein (pEGFP), as a model gene, was fully condensed with cationic PBAE to form the inner core of PBAE/pEGFP polycomplex. Methotrexate (MTX), as a model chemotherapy agent, was conjugated to pullulan by ester bond to synthesize polymeric prodrug of MTX-PL. MTX-PL was then adsorbed on the surface of PBAE/pEGFP polycomplex to form MTX-PL/PBAE/pEGFP nanoparticles with a classic core-shell structure. MTX-PL was also used as a hepatoma targeting moiety, because of its specific binding affinity for asialoglycoprotein receptor (ASGPR) overexpressed by human hepatoma HepG2 cells. MTX-PL/PBAE/pEGFP nanoparticles realized the efficient transfection of pEGFP in HepG2 cells and exhibited significant inhibitory effect on the cell proliferation. In HepG2 tumor-bearing nude mice, MTX-PL/PBAE/pEGFP nanoparticles were mainly distributed in the tumor after 24 h postintravenous injection. Altogether, this novel codelivery system with a strong hepatoma-targeting property achieved simultaneous delivery of gene and chemotherapy agent into tumor at both cellular and animal levels.
authors.affiliation: Tianjin Cancer Institute and Hospital, Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University , No. 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: An
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Yinsong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005936:Glucans / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D008727:Methotrexate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005936:Glucans; D011108:Polymers; C485184:enhanced green fluorescent protein; C507253:poly(beta-amino ester); D049452:Green Fluorescent Proteins; C009109:pullulan; D008727:Methotrexate
keywords: chemotherapy agent; gene; hepatoma; poly(β-amino) ester; pullulan