Nanoscale metal-organic frameworks (nMOFs) are excellent radiosensitizers for radiotherapy-radiodynamic therapy (RT-RDT). Herein, we report surface modification of a Hf-DBP nMOF for the co-delivery of a hydrophobic small-molecule toll-like receptor 7 agonist, imiquimod (IMD), and a hydrophilic macromolecule, anti-CD47 antibody (αCD47), for macrophage modulation and reversal of immunosuppression in tumors. IMD repolarizes immunosuppressive M2 macrophages to immunostimulatory M1 macrophages, while αCD47 blocks CD47 tumor cell surface marker to promote phagocytosis. Upon X-ray irradiation, IMD@Hf-DBP/αCD47 effectively modulates the immunosuppressive tumor microenvironment and activates innate immunity to orchestrate adaptive immunity when synergized with an anti-PD-L1 immune checkpoint inhibitor, leading to complete eradication of both primary and distant tumors on a bilateral colorectal tumor model. nMOFs thus provide a unique platform to co-deliver multiple immunoadjuvants for macrophage therapy to induce systematic immune responses and superb antitumor efficacy.

中文翻译：

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纳米级金属-有机框架共同提供 TLR-7 激动剂和抗 CD47 抗体以调节巨噬细胞和协调癌症免疫治疗

纳米级金属有机框架 (nMOF) 是放射治疗-放射动力治疗 (RT-RDT) 的优秀放射增敏剂。在此，我们报告了 Hf-DBP nMOF 的表面修饰，用于共同递送疏水性小分子 toll 样受体 7 激动剂咪喹莫特 (IMD) 和亲水性大分子抗 CD47 抗体 (αCD47)，用于巨噬细胞调节和逆转肿瘤中的免疫抑制。IMD 将免疫抑制性 M2 巨噬细胞复极化为免​​疫刺激性 M1 巨噬细胞，而 αCD47 阻断 CD47 肿瘤细胞表面标志物以促进吞噬作用。在 X 射线照射下，IMD@Hf-DBP/αCD47 与抗 PD-L1 免疫检查点抑制剂协同作用时，可有效调节免疫抑制性肿瘤微环境并激活先天免疫以协调适应性免疫，导致在双侧结直肠肿瘤模型上彻底根除原发性和远处肿瘤。因此，nMOFs 提供了一个独特的平台，可以共同提供多种免疫佐剂用于巨噬细胞治疗，以诱导系统性免疫反应和卓越的抗肿瘤功效。