期刊
ACS APPLIED MATERIALS & INTERFACES
卷 6, 期 21, 页码 18712-18720出版社
AMER CHEMICAL SOC
DOI: 10.1021/am504203x
关键词
pullulan; poly(beta-amino) ester; hepatoma; gene; chemotherapy agent
资金
- 973 program [2011CB933100]
- National Natural Science Foundation of China [81371671]
- National Science Fund for Distinguished Young Scholars [81125019]
This study designs a novel nanoparticle system with core shell structure based on pullulan and poly(beta-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 hepatomatargeting property achieved simultaneous delivery of gene and chemotherapy agent into tumor at both cellular and animal levels.
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