Enzyme-Responsive Charge-Reversal Polymer Mediated Effective Gene Therapy for Intraperitoneal Tumors.

Enzyme-Responsive Charge-Reversal Polymer Mediated Effective Gene Therapy for Intraperitoneal Tumors. Biomacromolecules. 2018 May 08;: Authors: Qiu N, Gao J, Liu Q, Wang J, Shen Y Abstract Gene therapy has demonstrated effectiveness in many genetic diseases as evidenced by recent clinical applications. Viral vectors have been extensively tested in clinical gene-therapy trials, but nonviral vectors such as cationic polymers or lipids are much less used due to their lower gene-transfection efficiencies. However, the advantages of nonviral vectors, such as easily tailored structures, nonimmunogenetics, and relatively low cost, still drive great efforts to improve their transfection efficiencies. A reverse question asks if nonviral vectors with current gene transfection efficiency can find application niches. Herein, we synthesized a cationic polymer, poly{N-[2-(acryloyloxy)ethyl]-N-[p-acetyloxyphenyl]-N,N-diethylammonium chloride} (PQDEA) as a gene-delivery carrier and compared it side by side with chemotherapy drugs for cancer treatment. PQDEA is rapidly hydrolyzed by intracellular esterases into anionic poly(acrylic acid) to give low cytotoxicity and fast release of DNA for expression. PQDEA formed stable complexes with DNA (PQDEA/DNA polyplexes), which were further coated with a lipid layer to make serum-stable lipidic polyplexes, LPQDEA/DNAs, for in vivo use. In an intraperitoneal tumor xenograft model mimicking late-stage metastati...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research