Bioorthogonal Chemistry-Guided Inhalable Nanoprodrug to Circumvent Cisplatin Resistance in Orthotopic Nonsmall Cell Lung Cancer.

Autor:	Tang L; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Yin Y; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Cao Y; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Liu H; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Qing G; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, P. R. China.; University of Chinese Academy of Sciences, National Center for Nanoscience and Technology of China, Beijing 100049, P. R. China., Fu C; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Li Z; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Zhu Y; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Shu W; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., He S; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Gao J; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Zhang Y; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Wang Z; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Bu J; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Li X; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China., Zhu M; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, P. R. China.; University of Chinese Academy of Sciences, National Center for Nanoscience and Technology of China, Beijing 100049, P. R. China., Liang XJ; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, P. R. China.; University of Chinese Academy of Sciences, National Center for Nanoscience and Technology of China, Beijing 100049, P. R. China., Wang W; State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P. R. China.; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, P. R. China.
Jazyk:	angličtina
Zdroj:	ACS nano [ACS Nano] 2024 Nov 19; Vol. 18 (46), pp. 32103-32117. Date of Electronic Publication: 2024 Nov 09.
DOI:	10.1021/acsnano.4c10947
Abstrakt:	Pulmonary delivery of anticancer therapeutics has shown encouraging performance in treating nonsmall cell lung cancer (NSCLC), which is characterized by high aggressiveness and poor prognosis. Cisplatin, a key member of the family of DNA alkylating agents, is extensively employed during NSCLC therapy. However, the development of chemoresistance and the occurrence of side effects severely impede the long-term application of cisplatin-based chemotherapies. Herein, we propose a meaningful strategy to precisely treat cisplatin-resistant NSCLC based on the combination of bioorthogonal chemistry with an inhalation approach. Ethacraplatin (EA-Pt), a platinum prodrug (IV), was synthesized and encapsulated in nitric oxide (NO)-containing micelles to overcome cisplatin chemoresistance. By further modifying bioorthogonal molecules in this nanoplatform (EA-Pt@M DBCO ), an improved targeting performance toward pulmonary cancerous regions is achieved after prelabeling with azide via inhalation. Upon entering acidic cancer cells, EA-Pt is swiftly released due to the pH sensitivity of bioorthogonal micelles, which enables its bifunctions to inhibit glutathione S -transferase activity and deplete intracellular glutathione, eventually reversing cisplatin resistance. Moreover, the released NO also improves the overall therapeutic outcome against NSCLC. Consequently, inhalable EA-Pt@M DBCO prelabeled by azide effectively inhibits the progression of cisplatin-resistant orthotopic NSCLC, offering a feasible nanostrategy to expand the treatment options for NSCLC.
Databáze:	MEDLINE
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