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<p>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&#xa0;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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月21日

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  • Na Kyeong Lee,
  • Chi-Pin James Wang,
  • Soo-Hyun Lee,
  • Nea Young Chun,
  • Yu Jin Oh,
  • Ulziituya Batjargal,
  • Min-Seok Kim,
  • WonJun Jang,
  • Han-Jun Kim,
  • Tae-Eun Park,
  • Wooram Park,
  • Chun Gwon Park,
  • Se-Na Kim

摘要

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.

Graphical abstract