Self-assembled lipid nanoparticles for ratiometric codelivery of cisplatin and siRNA targeting XPF to combat drug resistance in lung cancer.

Self-assembled lipid nanoparticles for ratiometric codelivery of cisplatin and siRNA targeting XPF to combat drug resistance in lung cancer. Chem Asian J. 2019 Mar 06;: Authors: Li C, Li T, Huang L, Yang M, Zhu G Abstract DNA damage repair through nucleotide excision repair (NER) pathway is one of the major reasons for the decreased antitumor efficacy of platinum-based anticancer drugs that have been widely applied in the clinic. Inhibiting intrinsic NER function may enhance the antitumor activity of cisplatin and conquer cisplatin resistance. Herein, we report the design, optimization, and application of a self-assembled lipid nanoparticle (LNP) system to simultaneously deliver a cisplatin prodrug together with siRNA targeting endonuclease XPF, a crucial component in the NER pathway. The LNP is able to efficiently encapsulate both platinum prodrugs and siRNA molecules with a tuned ratio. Both platinum prodrugs and XPF-targeted siRNA are efficiently carried into cells and released; the former damages DNA and the latter specifically down-regulates both mRNA and protein levels of XPF to potentiate the platinum drug, leading to enhanced expression levels of apoptosis markers and improved cytotoxicity in both cisplatin-sensitive and -resistant human lung cancer cells. Our results demonstrate an effective approach to utilize a multi-targeted nanoparticle system that can specifically silence NER-related gene to promote apoptosis induced by...
Source: Chemistry, an Asian Journal - Category: Chemistry Authors: Tags: Chem Asian J Source Type: research