MOF-Derived Oxygen-Deficient Titania-Mediated Photodynamic/Photothermal-Enhanced Immunotherapy for Tumor Treatment

Abstract

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_<i>x</i> 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. <i>In vitro</i>/<i>vivo</i> results demonstrate that MCT_<i>x</i> 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_<i>x</i> 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_<i>x</i> NP-mediated photodynamic- and photothermal-enhanced immunotherapy as an effective strategy for tumor treatment.