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.
摘要：
化疗是口腔鳞状细胞癌（OSCC）的主要治疗方法之一，尤其是作为手术或放疗后的联合模式方法。有限的疗效和严重的副作用极大地限制了化疗药物的临床应用。智能纳米药物的发展提供了新的研究方向,在某种程度上。然而,复杂载体组合物的参与不可避免地带来了生物安全性问题,并极大地限制了所报道的大多数纳米药物的“从床上到床上”翻译.在这项研究中,由两种三萜（甘草次酸，从药用植物中分离出GA和人参皂苷Rh2，Rh2），甘草,还有人参,用于OSCC的靶向和高效治疗。活性氧（ROS）自提供分子TK-GA2与ROS响应的硫代金属接头合成，并通过快速溶剂交换法与TK-GA2和Rh2制备前药。给药后,口腔肿瘤细胞竞争性地转运大量具有葡萄糖配体的前药。口腔肿瘤细胞内源性ROS促进GA和Rh2的释放。GA进一步诱发了大量ROS的产生，以帮助自我促进药物释放并增加氧化应激，与Rh2协同引起肿瘤细胞凋亡。总的来说,这种无载体的基于三萜的前药可能为设计针对OSCC的具有低全身毒性的有效化疗药物提供卓越的意见.
