Self-assembled Lipid Nanoparticles for Ratiometric Codelivery of Cisplatin and siRNA Targeting XPF to Combat Drug Resistance in Lung Cancer

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

2 Scopus Citations
View graph of relations

Detail(s)

Original languageEnglish
Pages (from-to)1570-1576
Journal / PublicationChemistry - An Asian Journal
Volume14
Issue number9
Online published6 Mar 2019
Publication statusPublished - 2 May 2019

Abstract

DNA damage repair through the 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 the 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 xeroderma pigmentosum group F (XPF), a crucial component in the NER pathway. The LNP is able to efficiently encapsulate both the platinum prodrug and siRNA molecules with a tuned ratio. Both platinum prodrug and XPF-targeted siRNA are efficiently carried into cells and released; the former damages DNA and the latter specifically downregulates 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 an NER-related gene to promote apoptosis induced by cisplatin, especially in cisplatin-refractory tumors.

Research Area(s)

  • cisplatin, drug delivery, gene silencing, nucleotide excision repair, resistance

Citation Format(s)

Self-assembled Lipid Nanoparticles for Ratiometric Codelivery of Cisplatin and siRNA Targeting XPF to Combat Drug Resistance in Lung Cancer. / Li, Cai; Li, Tianzhong; Huang, Linfeng; Yang, Mengsu; Zhu, Guangyu.

In: Chemistry - An Asian Journal, Vol. 14, No. 9, 02.05.2019, p. 1570-1576.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal