对于腹部或盆腔肿瘤患者，放疗可能会导致辐射诱发的肠道损伤（RIII），这是一种潜在的严重并发症，目前几乎没有有效的治疗选择。西格列汀 (SI) 是一种口服降血糖药物，具有抗细胞凋亡、抗氧化和抗炎活性，但其如何影响 RIII 相关结果尚未确定。在这项研究中，开发了一种基于 pH 响应金属有机框架的纳米颗粒平台，用于 SI 的传递 (SI@ZIF-8@MS NP)。这些纳米粒子掺入了 mPEG-b-PLLA (MS) 作为能够抵抗胃酸影响的试剂，并且能够释放 Zn2 离子。当暴露于酸性环境时，MS 能够有效地保护这些 SI@ZIF-8 NP 免于快速降解，从而随后在肠液中释放 SI 和 Zn2。值得注意的是，SI@ZIF-8@MS 治疗能够减轻这些小鼠中辐射引起的肠道菌群失调。恢复了辐射引起的细菌组成变化。总之，这些数据证明了 SI@ZIF-8@MS 能够防止 WAI 引起的小鼠肠道损伤，表明这些 NP 代表了一种多模式靶向治疗，可有效用于预防或治疗 RIII。© 2024。作者。

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.© 2024. The Author(s).