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A cationic prodrug/therapeutic gene nanocomplex for the synergistic treatment of tumors

Paper ID Volume ID Publish Year Pages File Format Full-Text
7555 556 2011 8 PDF Available
Title
A cationic prodrug/therapeutic gene nanocomplex for the synergistic treatment of tumors
Abstract

The combination of gene therapy and chemotherapy may increase the therapeutic efficacy in the treatment of patients. In this work, the cationic polymer prodrug/plasmid nanocomplexes were designed to in vivo synergistically treat drug-resistant breast tumors. Cationic β-cyclodextrin-polyethylenimine-Dox (PC-Dox) conjugates were prepared for carrying wt p53 plasmid in the form of PC-Dox/p53 nanocomplexes to achieve synergistic cancer therapeutic effects of drug and gene therapies. Such PC-Dox/p53 nanocomplexes ensure that both drug and gene can be delivered to the same cancer cells. The physicochemical properties and Dox release profiles of the PC-Dox conjugates, as well as their antitumor activities in vitro and in vivo, were determined. mRNA expression and western blot experiments also proved that co-delivery of Dox with wt p53 plasmid from PC-Dox/wt p53 complexes could promote wt p53 gene expression largely. By investigating anticancer efficacy via multi-drug resistant MCF-7/Adr breast cancer cells, it was found that PC-Dox/wt p53 complexes promoted the inhibition of tumor growth in vivo and prolonged the survival time of tumor-bearing mice. With the efficient ability to co-deliver drug and gene, such multifunctional PC-Dox/pDNA complexes should have great potential applications in cancer therapy.

Keywords
DNA; Gene therapy; Vectors; Transfection; Wild-type p53; Doxorubicin
First Page Preview
A cationic prodrug/therapeutic gene nanocomplex for the synergistic treatment of tumors
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 21, July 2011, Pages 4849–4856
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering