Resiquimod-loaded MOF525 enables synergistic photodynamic therapy and immunotherapy for colorectal cancer

Abstract

Metal-organic frameworks (MOFs) represent a class of materials with exceptional potential for biomedical applications. In this study, a synergistic platform integrating photodynamic therapy (PDT) and immunotherapy was developed by loading the Toll-like receptor 7/8 agonist resiquimod (R848) into MOF525, a porphyrin-based metal-organic framework (R848@MOF525). Owing to the intrinsic photosensitizing properties of porphyrinic ligands and the high porosity of MOF525, R848@MOF525 was able to effectively generate reactive oxygen species upon 660 nm laser irradiation and sustainably release R848. In vitro studies using R848@MOF525 showed significant PDT-mediated cytotoxicity in colon adenocarcinoma cells (CT26) and increased extracellular release of adenosine triphosphate, indicating potential induction of immunogenic cell deaths. R848@MOF525 also strongly promoted dendritic cell maturation in vitro, further highlighting their potential roles as simultaneous immunostimulatory adjuvants. In a subcutaneous CT26 tumor-bearing mouse model, PDT using R848@MOF525 was able to yield faster tumor regression than with MOF525. Furthermore, tumor rechallenge tests also showed no evident tumor growth up to 3 weeks, indicating that PDT using R848@MOF525 could induce a durable systemic antitumor immunity. Notably, under an extended treatment interval, PDT mediated by MOF525 failed to suppress tumor growth, whereas PDT using R848@MOF525 successfully maintained antitumor efficacy. Collectively, these findings highlight R848@MOF525 as a promising platform for colorectal cancer treatment, synergistically employing immunotherapy to enhance the antitumor efficacy of PDT.