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.
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Authors | Yuanyuan Liu, Yan Wang, Cong Zhang, Ping Zhou, Yang Liu, Tong An, Duxin Sun, Ning Zhang, Yinsong Wang |
Journal | ACS applied materials & interfaces
(ACS Appl Mater Interfaces)
Vol. 6
Issue 21
Pg. 18712-20
( 2014)
ISSN: 1944-8252 [Electronic] United States |
PMID | 25289563
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Drug Carriers
- Glucans
- Polymers
- enhanced green fluorescent protein
- poly(beta-amino ester)
- Green Fluorescent Proteins
- pullulan
- Methotrexate
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Topics |
- Animals
- Antineoplastic Agents
(chemistry, pharmacokinetics, pharmacology)
- Carcinoma, Hepatocellular
- Drug Carriers
(chemistry, pharmacokinetics)
- Glucans
(chemistry)
- Green Fluorescent Proteins
(genetics, metabolism)
- Hep G2 Cells
- Humans
- Liver Neoplasms
- Methotrexate
(chemistry, pharmacokinetics, pharmacology)
- Mice
- Mice, Nude
- Nanoparticles
(chemistry)
- Particle Size
- Polymers
(chemistry)
- Transfection
- Xenograft Model Antitumor Assays
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