Reduction/photo dual-responsive polymeric prodrug nanoparticles for programmed siRNA and doxorubicin delivery. (17th May 2018)

• Record Type: Journal Article
• Authors: Wu, Ming; Li, Jiong; Lin, Xinyi; Wei, Zuwu; Zhang, Da; Zhao, Bixing; Liu, Xiaolong; Liu, Jingfeng
• Is Part Of: Biomaterials science. Volume 6:Number 6(2018)
• Page Start: 1457
• Page End: 1468
• Publication Date: 2018-05-17
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c8bm00226f
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : A reduction/photo dual-responsive nanosystem for programmed P-gp siRNA and doxorubicin release was designed to optimize the efficacy of chemotherapy against multidrug resistance of cancer cells. Abstract : Dual and multi-stimuli responsive polymeric nanoparticles that respond to two or more signals can further improve drug release performance compared with nanoparticles that respond to a single stimulus. However, usage of such nanoparticles to deliver siRNA and chemotherapeutic drugs in a sequential manner are currently very rare; meanwhile, this technology is vital to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. By loading o -nitrobenzyl ester derivative caged DOX (DOC) into the inner poly(lactic- co -glycolic acid) (PLGA) core and adsorbing siRNA of P-gp protein onto the cationic polymeric shell derived from a disulfide-containing alkyl modified polyethylenimine (C16 -S-S-PEI), here, a reduction/photo dual responsive device (RPDRD) is successfully designed for programmed P-gp siRNA and doxorubicin delivery. The dual-stimuli design of the RPDRD allows tumor microenvironment-specific and rapid release of P-gp siRNA triggered by the enrichment of reducing agent glutathione (GSH, up to 10 mM) for reversal of drug resistance by initially suppressing P-gp protein expression in MCF/ADR cells and then selectively triggering drug release by external light for chemotherapy afterwards. The sequential release behavior of P-gp siRNA and DOX can be demonstrated both in vitro and in vivo, thus enhancing the intracellular drug retention and optimizing the chemotherapy efficacy of DOX by silencing P-gp; this strategy may have extensive application prospects in MDR cancer treatment in future.