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

作者:Lu, Xiao; Wang, Qing-Qing; Xu, Fu-Jian*; Tang, Gu-Ping; Yang, Wan-Tai
来源:Biomaterials, 2011, 32(21): 4849-4856.
DOI:10.1016/j.biomaterials.2011.03.022

摘要

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 beta-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.