Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznanskiego 8, Poznan, 61-614, Poland.
Center for Advanced Technologies, Adam Mickiewicz University, Uniwersytetu Poznanskiego 10, Poznan, 61-614, Poland.
Sci Rep. 2024 Sep 27;14(1):22343. doi: 10.1038/s41598-024-73266-2.
Meta-tetra(hydroxyphenyl)chlorin (m-THPC) is among the most potent photosensitizers, known for its high singlet oxygen generation efficiency. However, its clinical effectiveness in photodynamic therapy (PDT) is compromised by its propensity to aggregate in aqueous solutions, adversely affecting its photophysical properties and therapeutic potential. A series of spectroscopic techniques, including UV-Vis absorption, fluorescence spectroscopy, and laser flash photolysis, revealed that m-THPC exhibits significant aggregation, particularly in MeOH-PBS mixtures with MeOH content below 30%. This aggregation adversely affects its photophysical properties leading to reduced fluorescence quantum yield and most importantly reducing its singlet oxygen quantum yield. This study introduces the use of bovine serum albumin (BSA) to counteract the aggregation of m-THPC, aiming to enhance its solubility, stability, and efficacy in physiological settings. Through advanced spectroscopic analyses we demonstrated that the m-THPC@BSA complex exhibits restored photophysical properties characteristic for monomeric form. Notably, the complex showed a significant restoration of the singlet oxygen quantum yield (Φ = 0.21) compared to aggregated m-THPC. These results underscore the potential of BSA to preserve the monomeric form of m-THPC, mitigating aggregation-induced losses in singlet oxygen production. Our findings suggest that BSA-mediated delivery systems could play a crucial role in optimizing the clinical utility of hydrophobic photosensitizers like m-THPC.
间四羟苯基氯（m-THPC）是最有效的光敏剂之一，以其高效的单线态氧产生效率而闻名。然而，其在光动力疗法（PDT）中的临床效果受到其在水溶液中易于聚集的影响，这会对其光物理性质和治疗潜力产生不利影响。一系列光谱技术，包括紫外-可见吸收、荧光光谱和激光闪光光解，表明 m-THPC 表现出明显的聚集，特别是在甲醇-PBS 混合物中甲醇含量低于 30%时。这种聚集会影响其光物理性质，导致荧光量子产率降低，最重要的是降低其单线态氧量子产率。本研究介绍了使用牛血清白蛋白（BSA）来对抗 m-THPC 的聚集，旨在提高其在生理环境中的溶解度、稳定性和疗效。通过先进的光谱分析，我们证明了 m-THPC@BSA 复合物具有恢复的单体形式的光物理性质。值得注意的是，与聚集的 m-THPC 相比，该复合物表现出单线态氧量子产率（Φ=0.21）的显著恢复。这些结果强调了 BSA 保留 m-THPC 单体形式的潜力，减轻了聚集诱导的单线态氧产生损失。我们的研究结果表明，BSA 介导的递送系统在优化疏水性光敏剂如 m-THPC 的临床应用方面可能发挥关键作用。
