Hybrid chalcogen bonds in prodrug nanoassemblies provides dual redox-responsivity in the tumor microenvironment.

Autor: Liu T; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Li L; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Wang S; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Dong F; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Zuo S; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Song J; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Wang X; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Lu Q; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Wang H; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Zhang H; Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Cheng M; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Liu X; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., He Z; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China., Sun B; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China. sunbingjun_spy@sina.com., Sun J; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, 110016, Shenyang, People's Republic of China. sunjin@syphu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 24; Vol. 13 (1), pp. 7228. Date of Electronic Publication: 2022 Nov 24.
DOI: 10.1038/s41467-022-35033-7
Abstrakt: Sulfur bonds, especially trisulfide bond, have been found to ameliorate the self-assembly stability of homodimeric prodrug nanoassemblies and could trigger the sensitive reduction-responsive release of active drugs. However, the antitumor efficacy of homodimeric prodrug nanoassemblies with single reduction-responsivity may be restricted due to the heterogeneous tumor redox microenvironment. Herein, we replace the middle sulfur atom of trisulfide bond with an oxidizing tellurium atom or selenium atom to construct redox dual-responsive sulfur-tellurium-sulfur and sulfur-selenium-sulfur hybrid chalcogen bonds. The hybrid chalcogen bonds, especially the sulfur-tellurium-sulfur bond, exhibit ultrahigh dual-responsivity to both oxidation and reduction conditions, which could effectively address the heterogeneous tumor microenvironment. Moreover, the hybrid sulfur-tellurium-sulfur bond promotes the self-assembly of homodimeric prodrugs by providing strong intermolecular forces and sufficient steric hindrance. The above advantages of sulfur-tellurium-sulfur bridged homodimeric prodrug nanoassemblies result in the improved antitumor efficacy of docetaxel with satisfactory safety. The exploration of hybrid chalcogen bonds in drug delivery deepened insight into the development of prodrug-based chemotherapy to address tumor redox heterogeneity, thus enriching the design theory of prodrug-based nanomedicines.
(© 2022. The Author(s).)
Databáze: MEDLINE
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