Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, Shanghai, 200438, China.
Department of Inorganic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
Biomaterials. 2022 May;284:121467. doi: 10.1016/j.biomaterials.2022.121467. Epub 2022 Mar 18.
Despite that photodynamic therapy (PDT) has been applied for the treatment of cancer and skin diseases for more than two decades, all clinically used photodynamic agents (PDAs) suffer the drawback of skin phototoxicity of PDAs, which requires patients to avoid exposure to natural light for weeks after treatment, but has so far lacked effective suppression methods. Here, we report that three-dimensional diamondoid supramolecular organic frameworks (SOFs), that possess well-defined 2.1-nm porosity, can be used to suppress the skin phototoxicity of Photofrin, HiPorfin and Talaporfin, three porphyrin-based PDAs which clinically receive the most wide applications by injecting SOF after PDT, via an adsorption and retention mechanism. Fluorescence and dynamic light scattering experiments confirm that the SOFs have strong interaction with PDAs, and can adsorb PDAs at a micromolar concentration, whereas dialysis experiments support that the adsorption leads to an important retention effect. In vitro and in vivo experiments reveal that SOFs have high biocompatibility. Studies with healthy and tumor-bearing mouse models demonstrate that, when the PDAs are administrated at a dose comparable with the clinical one, SOF can remarkably suppress sunlight-induced skin phototoxicity, whereas the PDT efficacy of mice treated with SOF post-PDT is maintained. This work provides an efficient strategy for the improvement of the safety of clinically used PDAs.
尽管光动力疗法（PDT）已经应用于癌症和皮肤病的治疗超过二十年，但所有临床使用的光动力试剂（PDAs）都存在 PDA 皮肤光毒性的缺点，这要求患者在治疗后数周内避免暴露在自然光下，但迄今为止缺乏有效的抑制方法。在这里，我们报告了具有明确定义的 2.1nm 孔隙率的三维金刚烷超分子有机框架（SOF），可以通过在 PDT 后注射 SOF 来抑制 Photofrin、HiPorfin 和 Talaporfin 三种临床上应用最广泛的基于卟啉的 PDAs 的皮肤光毒性，其机制是通过吸附和保留。荧光和动态光散射实验证实 SOFs 与 PDAs 具有很强的相互作用，可以在微摩尔浓度下吸附 PDAs，而透析实验支持这种吸附导致的重要保留效果。体外和体内实验表明 SOFs 具有很高的生物相容性。在健康和荷瘤小鼠模型中的研究表明，当 PDAs 的剂量与临床剂量相当时，SOF 可以显著抑制阳光诱导的皮肤光毒性，而用 SOF 处理后的 PDT 对小鼠的 PDT 疗效得以维持。这项工作为提高临床使用的 PDAs 的安全性提供了一种有效的策略。
