Experimental Biomolecular Physics, Dept. Applied Physics, Royal Institute of Technology (KTH), Albanova Univ Center, 106 91, Stockholm, Sweden.
Sci Rep. 2023 Oct 6;13(1):16829. doi: 10.1038/s41598-023-43625-6.
Photodynamic therapy (PDT) fundamentally relies on local generation of PDT precursor states in added photosensitizers (PS), particularly triplet and photo-radical states. Monitoring these states in situ can provide important feedback but is difficult in practice. The states are strongly influenced by local oxygenation, pH and redox conditions, often varying significantly at PDT treatment sites. To overcome this problem, we followed local PDT precursor state populations of PS compounds, via their fluorescence intensity response to systematically varied excitation light modulation. Thereby, we could demonstrate local monitoring of PDT precursor states of methylene blue (MB) and IRdye700DX (IR700), and determined their transitions rates under different oxygenation, pH and redox conditions. By fiber-optics, using one fiber for both excitation and fluorescence detection, the triplet and photo-radical state kinetics of locally applied MB and IR700 could then be monitored in a tissue sample. Finally, potassium iodide and ascorbate were added as possible PDT adjuvants, enhancing intersystem crossing and photoreduction, respectively, and their effects on the PDT precursor states of MB and IR700 could be locally monitored. Taken together, the presented procedure overcomes current methodological limitations and can offer feedback, guiding both excitation and PDT adjuvant application, and thereby more efficient and targeted PDT treatments.
光动力疗法（PDT）从根本上依赖于添加的光敏剂（PS）中 PDT 前体状态的局部生成，特别是三重态和光自由基状态。原位监测这些状态可以提供重要的反馈，但在实践中却很困难。这些状态强烈受到局部氧合、pH 值和氧化还原条件的影响，在 PDT 治疗部位经常有很大的变化。为了克服这个问题，我们通过 PS 化合物的荧光强度对系统变化的激发光调制的响应，跟踪其局部 PDT 前体状态。由此，我们可以证明对亚甲蓝（MB）和 IRdye700DX（IR700）的 PDT 前体状态进行局部监测，并确定它们在不同的氧合、pH 值和氧化还原条件下的转变速率。通过光纤，使用一根光纤同时进行激发和荧光检测，我们可以监测局部应用的 MB 和 IR700 的三重态和光自由基状态动力学。最后，添加碘化钾和抗坏血酸作为可能的 PDT 佐剂，分别增强系间窜跃和光还原，并且可以局部监测它们对 MB 和 IR700 的 PDT 前体状态的影响。总之，所提出的方法克服了当前方法学的限制，可以提供反馈，指导激发和 PDT 佐剂的应用，从而实现更有效和有针对性的 PDT 治疗。
