Xiao Bo, Liao Yueyue, Zhang Jinyu, Chen Ke, Feng Guangwei, Feng Jian, Zhang Chunlin
School of Basic Medical Sciences/School of Medical Humanities, Guizhou Medical University, Guiyang 550025, China.
Int J Mol Sci. 2024 Dec 4;25(23):13037. doi: 10.3390/ijms252313037.
Porphyrins serve as photosensitizers (PS) in the realm of cancer photodynamic therapy (PDT). Upon excitation by laser light, porphyrins are capable of converting molecular oxygen into highly cytotoxic singlet oxygen (O). However, the rigid π-conjugated structure of porphyrins frequently results in the formation of aggregates in aqueous solutions, which leads to the self-quenching of the excited state. Cucurbit[n]urils exhibit the capacity to stably bind with porphyrins via host-guest interactions, effectively inhibiting their aggregation and potentially enhancing the therapeutic efficacy of PDT. In this study, water-soluble tetramethyl cucurbit[6]uril (TMeQ[6]) was selected as the host, while four propionic acid group-appended porphyrin cationic (TPPOR) was utilized as guests to construct a supramolecular photosensitizer (TPPOR-2TMeQ[6]) in a molar ratio of 2:1. Further experimental findings demonstrate that the presence of TMeQ[6] inhibits the aggregation of TPPOR through non-covalent interactions. This inhibition reduces the energy difference between the excited singlet and triplet states, thereby enhancing the conversion efficiency of O. Moreover, TPPOR-2TMeQ[6] exhibits favorable biocompatibility and minimal dark toxicity against breast cancer cells (4T1). Upon intracellular excitation, the levels of reactive oxygen species (ROS) significantly increase, inducing oxidative stress in 4T1 cells and leading to apoptosis. Consequently, the findings of this study suggest that the enhanced photosensitization achieved through this supramolecular approach is likely to promote the anticancer therapeutic effects of PDT, thereby broadening the application prospects of porphyrins within PDT systems.
在癌症光动力疗法（PDT）领域，卟啉用作光敏剂（PS）。在激光激发下，卟啉能够将分子氧转化为具有高度细胞毒性的单线态氧（O）。然而，卟啉的刚性π共轭结构常常导致其在水溶液中形成聚集体，这会导致激发态的自猝灭。葫芦[n]脲能够通过主客体相互作用与卟啉稳定结合，有效抑制其聚集，并有可能提高PDT的治疗效果。在本研究中，选择水溶性四甲基葫芦[6]脲（TMeQ[6]）作为主体，同时使用四个带有丙酸基团的卟啉阳离子（TPPOR）作为客体，以2:1的摩尔比构建超分子光敏剂（TPPOR-2TMeQ[6]）。进一步的实验结果表明，TMeQ[6]的存在通过非共价相互作用抑制了TPPOR的聚集。这种抑制作用减小了激发单线态和三线态之间的能量差，从而提高了O的转化效率。此外，TPPOR-2TMeQ[6]对乳腺癌细胞（4T1）表现出良好的生物相容性和最小的暗毒性。在细胞内激发后，活性氧（ROS）水平显著增加，在4T1细胞中诱导氧化应激并导致细胞凋亡。因此，本研究结果表明，通过这种超分子方法实现的增强光敏化作用可能会促进PDT的抗癌治疗效果，从而拓宽卟啉在PDT系统中的应用前景。
