Metal-organic-framework-based sitagliptin-release platform for multieffective radiation-induced intestinal injury targeting therapy and intestinal flora protective capabilities

In patients with abdominal or pelvic tumors, radiotherapy can result in radiation-induced intestinal injury (RIII), a potentially severe complication for which there are few effective therapeutic options. Sitagliptin (SI) is an oral hypoglycemic drug that exhibits antiapoptotic, antioxidant, and anti-inflammatory activity, but how it influences RIII-associated outcomes has yet to be established. In this study, a pH-responsive metal-organic framework-based nanoparticle platform was developed for the delivery of SI (SI@ZIF-8@MS NP). These NPs incorporated mPEG-b-PLLA (MS) as an agent capable of resisting the effects of gastric acid, and are capable of releasing Zn²⁺ ions. MS was able to effectively shield these SI@ZIF-8 NPs from rapid degradation when exposed to an acidic environment, enabling the subsequent release of SI and Zn²⁺ within the intestinal fluid. Notably, SI@ZIF-8@MS treatment was able to mitigate radiation-induced intestinal dysbiosis in these mice. restored radiation-induced changes in Bacterial composition. In summary, these data demonstrate the ability of SI@ZIF-8@MS to protect against WAI-induced intestinal damage in mice, suggesting that these NPs represent a multimodal targeted therapy that can effectively be used in the prevention or treatment of RIII.

Radiation-induced intestinal injury; Sitagliptin; Whole abdominal irradiation; ZIF-8.