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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\u2010assembled 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\u2010targeted 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\u2010sensitive and \u2010resistant human lung cancer cells. Our results demonstrate an effective approach to utilize a multi\u2010targeted nanoparticle system that can specifically silence an NER\u2010related gene to promote apoptosis induced by cisplatin, especially in cisplatin\u2010refractory tumors.<\/jats:p>","DOI":"10.1002\/asia.201900005","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T21:59:16Z","timestamp":1551909556000},"page":"1570-1576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Self\u2010assembled Lipid Nanoparticles for Ratiometric Codelivery of Cisplatin and siRNA Targeting XPF to Combat Drug Resistance in Lung Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Cai","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemistry City University of Hong Kong  83 Tat Chee Ave Kowloon Tong, Hong Kong SAR China"},{"name":"City University of Hong Kong Shenzhen Research Institute  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences City University of Hong Kong  83 Tat Chee Ave Kowloon Tong, Hong Kong SAR China"},{"name":"City University of Hong Kong Shenzhen Research Institute  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences City University of Hong Kong  83 Tat Chee Ave Kowloon Tong, Hong Kong SAR China"},{"name":"City University of Hong Kong Shenzhen Research Institute  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengsu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences City University of Hong Kong  83 Tat Chee Ave Kowloon Tong, Hong Kong SAR China"},{"name":"City University of Hong Kong Shenzhen Research Institute  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4710-7070","authenticated-orcid":false,"given":"Guangyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Chemistry City University of Hong Kong  83 Tat Chee Ave Kowloon Tong, Hong Kong SAR China"},{"name":"City University of Hong Kong Shenzhen Research Institute  China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1691"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.384"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08467"},{"key":"e_1_2_7_4_1","unstructured":"\u00a0"},{"key":"e_1_2_7_5_2","first-page":"4899","volume":"62","author":"Furuta T.","year":"2002","journal-title":"Cancer Res."},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20134"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00441-X"},{"key":"e_1_2_7_8_1","first-page":"4760","volume":"55","author":"Nie Z. 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