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.
authors: Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors: Xiao
authors: X
authors: Lu
authors: Qing-Qing
authors: QQ
authors: Wang
authors: Fu-Jian
authors: FJ
authors: Xu
authors: Gu-Ping
authors: GP
authors: Tang
authors: Wan-Tai
authors: WT
authors: Yang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000628:therapy*; D002412:Cations / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry* / Q000627:therapeutic use*; D011355:Prodrugs / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D002412:Cations; D004337:Drug Carriers; D011355:Prodrugs; D004317:Doxorubicin