posted on 2014-11-12, 00:00authored byYuanyuan Liu, Yan Wang, Cong Zhang, Ping Zhou, Yang Liu, Tong An, Duxin Sun, Ning Zhang, Yinsong Wang
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.