Programmable "triple attack" cancer therapy through in situ activation of disulfiram toxification combined with phototherapeutics.

Effectively and completely eliminating residual tumor cells is the key to reducing the risk of tumor metastasis and recurrence. Designing an "ideal" nanoplatform for programmable cancer therapy has great prospects for completely eliminating residual tumor cells. Herein, an intelligent nanoplatform of disulfiram (DSF)-loaded CuS-tannic acid nanohexahedrons (denoted as "DSF-CuS@TA") with thermal- and pH-sensitive degradation, as well as near-infrared (NIR-II) phototherapeutics properties, was constructed. And then, it was employed for in situ DSF toxification activation programmable "triple attack" cancer therapy. After accumulating in the tumor, DSF-CuS@TA first releases the loaded Cu(DTC)2, and simultaneously degrades and releases Cu2+ and DSF under mildly acidic stimulation to trigger instant intratumoral Cu(DTC)2 chelation, thereby achieving the "first strike." Next, under irradiation by a NIR-II laser, light energy is converted into heat to generate NIR-II photothermal therapy, thereby achieving the second strike. Subsequently, under thermal stimulation, DSF-CuS@TA degrades further, triggering the chelation of Cu(DTC)2 for a second time to reach the third strike. As expected, in vitro and in vivo studies showed that the synergistic integration of DSF-based programmed chemotherapy and NIR-II phototherapeutics could achieve effective tumor removal. Therefore, we propose a novel type of programmed therapy against cancer by designing a nanoplatform via "nontoxicity-to-toxicity" chemical chelation transformation.

Current advances in environmental stimuli regulating the glycyrrhizic acid biosynthesis pathway.

Glycyrrhizic acid, the main active ingredient of licorice, has good antibacterial, anti-tumor, anti-viral, anti-inflammatory, and immunostimulatory activities. However, the content of glycyrrhizic acid fluctuates greatly in different licorice cultivars, and production depends on plant sources, which greatly limits its development and applications. Therefore, increasing glycyrrhizic acid content has become a research priority. In recent years, regulation of the glycyrrhizic acid biosynthesis pathway has been analyzed, the downstream synthesis pathway in licorice has been fully investigated, some key genes have been cloned, polymorphisms have been studied, and the content of glycyrrhizic acid was shown to be regulated by environmental stimuli. This work has provided a basis for studying the regulation mechanism of the glycyrrhizic acid synthesis pathway. This review summarizes and discusses relevant research to provide a current understanding of the glycyrrhizic acid synthesis pathway and its regulation in licorice.