Jie Zhong, Guantong He, Xu Ma, Jinhai Ye, Zhuo-Ying Tao, Zhongxian Li, Fuxue Zhang, Peijian Feng, Yuji Wang, Xinmiao Lan, Yu-Xiong Su
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引用次数: 0
Abstract
Chemotherapy is one of the main treatments for oral squamous cell carcinoma (OSCC), especially as a combined modality approach with and after surgery or radiotherapy. Limited therapeutic efficiency and serious side effects greatly restrict the clinical performance of chemotherapeutic drugs. The development of smart nanomedicines has provided new research directions, to some extent. However, the involvement of complex carrier compositions inevitably brings biosafety concerns and greatly limits the "bench-to-bed" translation of most nanomedicines reported. In this study, a carrier-free self-assembled prodrug was fabricated by two triterpenes (glycyrrhetinic acid, GA and ginsenoside Rh2, Rh2) isolated from medicinal plants, licorice, and ginseng, for the targeted and highly effective treatment of OSCC. Reactive oxygen species (ROS) self-supplied molecule TK-GA2 was synthesized with ROS-responsive thioketal linker and prodrug was prepared by a rapid-solvent-exchange method with TK-GA2 and Rh2. After administration, oral tumor cells transported large amounts of prodrugs with glucose ligands competitively. Endogenous ROS in oral tumor cells then promoted the release of GA and Rh2. GA further evoked the generation of a large number of ROS to help self-boosted drug release and increase oxidative stress, synergistically causing tumor cell apoptosis with Rh2. Overall, this carrier-free triterpene-based prodrug might provide a preeminent opinion on the design of effective chemotherapeutics with low systemic toxicity against OSCC.
期刊介绍:
ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.