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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.
AuthorsYuanyuan Liu, Yan Wang, Cong Zhang, Ping Zhou, Yang Liu, Tong An, Duxin Sun, Ning Zhang, Yinsong Wang
JournalACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 6 Issue 21 Pg. 18712-20 ( 2014) ISSN: 1944-8252 [Electronic] United States
PMID25289563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • Glucans
  • Polymers
  • enhanced green fluorescent protein
  • poly(beta-amino ester)
  • Green Fluorescent Proteins
  • pullulan
  • Methotrexate
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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