Resiquimod-encapsulated MOF525 for Sustained Immunostimulant Release and Synergistic Photodynamic– Immunotherapy in Colorectal Cancer

Metal-organic frameworks (MOFs) represent a novel class of materials with exceptional potential for biomedical applications. In this study, we present MOF525, a porphyrin-based MOF, as a dual-functional platform for photodynamic therapy (PDT) and immunotherapy in the treatment of colorectal cancer. MOF525 encapsulates Resiquimod (R848), a potent Toll-like receptor 7/8 agonist, thereby establishing a synergistic therapeutic strategy. Upon light exposure, MOF525 efficiently generates reactive oxygen species, leading to localized tumor cell death and the release of tumor-associated antigens. Simultaneously, the sustained release of R848 enhances immune activation, effectively overcoming tumor-induced immunosuppression. This dual approach addresses the limitations of conventional PDT and immunotherapy while maximizing their synergistic potential. In vitro and in vivo studies demonstrate that the combination of PDT and R848-loaded MOF525 significantly inhibits tumor growth and elicits a robust antitumor immune response. Moreover, the therapeutic synergy between PDT and R848 is more pronounced under a less frequent treatment regimen, highlighting the potential clinical applicability of this dual-functional nanoplatform. These findings underscore the promise of R848-loaded MOF525 as a versatile and effective therapeutic strategy for colorectal cancer by integrating photodynamic tumor ablation with innate immune stimulation.