Colorectal cancer (CRC) is a leading cause of cancer-related death for both men and women, highlighting the need for new treatment strategies. Advanced disease is often treated with a combination of radiation and cytotoxic agents, such as DNA damage repair inhibitors and DNA damaging agents. To optimize the therapeutic window of these multimodal therapies, advanced nanomaterials have been investigated to deliver sensitizing agents or enhance local radiation dose deposition. In this study, we demonstrate the feasibility of employing an inflammation targeting nanoscale metal-organic framework (nMOF) platform to enhance CRC treatment. This novel formulation incorporates a fucoidan surface coating to preferentially target P-selectin, which is over-expressed or translocated in irradiated tumors. Using this radiation stimulated delivery strategy, a combination PARP inhibitor (talazoparib) and chemotherapeutic (temozolomide) drug-loaded hafnium and 1,4-dicarboxybenzene (Hf-BDC) nMOF was evaluated both in vitro and in vivo. Significantly, these drug-loaded P-selectin targeted nMOFs (TT@Hf-BDC-Fuco) show improved tumoral accumulation over multiple controls and subsequently enhanced therapeutic effects. The integrated radiation and nanoformulation treatment demonstrated improved tumor control (reduced volume, density, and growth rate) and increased survival in a syngeneic CRC mouse model. Overall, the data from this study support the continued investigation of radiation-priming for targeted drug delivery and further consideration of nanomedicine strategies in the clinical management of advanced CRC.

结直肠癌 (CRC) 是男性和女性癌症相关死亡的主要原因，这凸显了对新治疗策略的需求。晚期疾病通常采用放射和细胞毒剂的组合治疗，例如 DNA 损伤修复抑制剂和 DNA 损伤剂。为了优化这些多模式疗法的治疗窗口，已经研究了先进的纳米材料以递送敏化剂或增强局部辐射剂量沉积。在这项研究中，我们证明了使用炎症靶向纳米级金属有机框架 (nMOF) 平台来增强 CRC 治疗的可行性。这种新型配方结合了褐藻糖胶表面涂层以优先靶向P-选择素，在受照射的肿瘤中过度表达或易位。使用这种辐射刺激的递送策略，在体外和体内评估了 PARP 抑制剂（他唑帕尼）和化疗药物（替莫唑胺）载药铪和 1,4-二羧基苯 (Hf-BDC) nMOF 的组合。值得注意的是，这些载药P-选择素靶向 nMOFs (TT@Hf-BDC-Fuco) 显示出比多个对照更好的肿瘤积累并随后增强了治疗效果。在同基因 CRC 小鼠模型中，综合辐射和纳米制剂治疗显示出改善的肿瘤控制（减小的体积、密度和生长速率）和增加的存活率。总体而言，这项研究的数据支持继续研究用于靶向药物递送的辐射引发，并进一步考虑在晚期 CRC 临床管理中的纳米医学策略。