Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy has been largely limited by a weak immune response and an immunosuppressive tumor microenvironment. Herein, we report a metal–organic framework (MOF)-derived titanium oxide nanoparticle (MCT_x NP) as an immune booster that can greatly improve the immunotherapy efficacy by inducing “immunogenic cell death” (ICD) and remodeling the tumor microenvironment. The NPs, inheriting the characteristic structure of MIL-125 and enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency and a reactive oxygen species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, the NPs can release O₂ and reduce glutathione (GSH) in the tumor environment, showcasing their potential to reverse the immunosuppressive microenvironment. In vitro/vivo results demonstrate that MCT_x NPs directly kill tumor cells and effectively eliminate primary tumors by exerting dual photodynamic/photothermal therapy under a single NIR irritation. At the same time, MCT_x NPs augment the PD-L1 blockade efficacy by potently inducing ICDs and reversing the immunosuppressive tumor microenvironment, including promoting dendritic cell (DC) maturation, decreasing regulatory T cells (Tregs)’ infiltration, and increasing cytotoxic T lymphocytes (CTLs) and helper T cells (Ths), resulting in effective distant tumor suppression. This work highlights MCT_x NP-mediated photodynamic- and photothermal-enhanced immunotherapy as an effective strategy for tumor treatment.

中文翻译：

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MOF 衍生的缺氧二氧化钛介导的光动力/光热增强免疫疗法用于肿瘤治疗


免疫疗法已成为一种革命性的癌症治疗方式。然而，其功效在很大程度上受到免疫反应较弱和免疫抑制肿瘤微环境的限制。在此，我们报道了一种金属有机框架（MOF）衍生的二氧化钛纳米颗粒（MCT _x NP）作为免疫增强剂，可以通过诱导“免疫原性细胞死亡”（ICD）和重塑肿瘤微环境。这些纳米粒子继承了 MIL-125 的特征结构并富含氧空位 (OV)，在近红外 (NIR) 激活时表现出高光热转换效率和活性氧 (ROS) 生成率。此外，纳米颗粒可以释放O ₂ 并减少肿瘤环境中的谷胱甘肽（GSH），显示出它们逆转免疫抑制微环境的潜力。体外/体内结果表明，MCT _x NPs 通过在单次近红外刺激下发挥双重光动力/光热治疗作用，直接杀死肿瘤细胞并有效消除原发肿瘤。同时，MCT _x NPs 通过有效诱导 ICD 和逆转免疫抑制肿瘤微环境来增强 PD-L1 阻断功效，包括促进树突状细胞 (DC) 成熟、减少调节性 T 细胞 (Treg) 浸润，并增加细胞毒性 T 淋巴细胞 (CTL) 和辅助 T 细胞 (Ths)，从而有效抑制远处肿瘤。这项工作强调了 MCT _x NP 介导的光动力和光热增强免疫疗法作为肿瘤治疗的有效策略。