Ginger-derived vesicle-like nanoparticles loaded with curcumin to alleviate ionizing radiation-induced intestinal damage via gut microbiota regulation
Xinrui Zhang, Qian Cui, Yin Li, Jin Zhu, Yinghua Mao, Rong Yin, Hao Shao, Wenjing Wang, Xuewei Sun, Zhuohan Zhang, Chunyan Gu, Mingyan Zhang, Ruonan Zhang, Lu Han, Zhipeng Cai, Hong Li, Zhan Yang
Abstract
Emerging insights have been approached that gut microbiota act as a critical regulator for ionizing radiation (IR)-induced damage. Herein, an available strategy has been explored to shape gut microbiota for radioprotection by loading curcumin (Cur) into ginger-derived vesicle-like nanoparticles (GDNs). Engineered biomimetic nanovesicles (GDN-Cur) exhibited superb stability in the gastrointestinal tract, thereby significantly enhancing the oral bioavailability of Cur. Consequently, the intrinsic antioxidative, anti-inflammatory, and anti-apoptotic properties of GDNs and Cur granted this nanosystem exceptional protective effect against IR-induced injuries, especially in mitigating intestinal damage. Particularly, the dysbacteriosis triggered by IR could be counteracted through the oral administration of GDN-Cur, resulting in gut microbiota regulation-mediated syndrome mitigation. Furthermore, elevated abundances of Akkermansia muciniphila (A. muciniphila), a bacterial strain of Akkermansia taxa responsive to GDN-Cur, especially their supernatants, were associated with post-radiation protection of intestinal function. This beneficial effect was attributed to the identified radioprotective metabolites secreted by A. muciniphila, such as tanespimycin (17-AAG), which was demonstrated to deactivate AKT/NF-κB signaling pathway. These findings reveal the impact of plant products on radioprotective microbes and metabolites to target host processes and alleviate IR-induced intestinal damage, shedding light on new insights in the development of novel radioprotectants.