Satellite-Type Sulfur Atom Distribution in Trithiocarbonate Bond-Bridged Dimeric Prodrug Nanoassemblies: Achieving Both Stability and Activatability.

Autor: Li L; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Liu T; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Zuo S; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Li Y; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Zhao E; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Lu Q; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Wang D; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Sun Y; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., He Z; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Sun B; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China., Sun J; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2024 Jan; Vol. 36 (4), pp. e2310633. Date of Electronic Publication: 2023 Nov 29.
DOI: 10.1002/adma.202310633
Abstrakt: Homodimeric prodrug nanoassemblies (HDPNs) hold promise for improving the delivery efficiency of chemo-drugs. However, the key challenge lies in designing rational chemical linkers that can simultaneously ensure the chemical stability, self-assembly stability, and site-specific activation of prodrugs. The "in series" increase in sulfur atoms, such as trisulfide bond, can improve the assembly stability of HDPNs to a certain extent, but limits the chemical stability of prodrugs. Herein, trithiocarbonate bond (─SC(S)S─), with a stable "satellite-type" distribution of sulfur atoms, is developed via the insertion of a central carbon atom in trisulfide bonds. ─SC(S)S─ bond effectively addresses the existing predicament of HDPNs by improving the chemical and self-assembly stability of homodimeric prodrugs while maintaining the on-demand bioactivation. Furthermore, ─SC(S)S─ bond inhibits antioxidant defense system, leading to up-regulation of the cellular ROS and apoptosis of tumor cells. These improvements of ─SC(S)S─ bond endow the HDPNs with in vivo longevity and tumor specificity, ultimately enhancing the therapeutic outcomes. ─SC(S)S─ bond is, therefore, promising for overcoming the bottleneck of HDPNs for efficient oncological therapy.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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