Menilli Luca, Monteiro Ana R, Lazzarotto Silvia, Morais Filipe M P, Gomes Ana T P C, Moura Nuno M M, Fateixa Sara, Faustino Maria A F, Neves Maria G P M S, Trindade Tito, Miolo Giorgia
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
Department of Biology, University of Padova, 35131 Padova, Italy.
Pharmaceutics. 2021 Sep 18;13(9):1512. doi: 10.3390/pharmaceutics13091512.
The development of new photodynamic therapy (PDT) agents designed for bladder cancer (BC) treatments is of utmost importance to prevent its recurrence and progression towards more invasive forms. Here, three different porphyrinic photosensitizers (PS) (TMPyP, Zn-TMPyP, and P1-C) were non-covalently loaded onto graphene oxide (GO) or graphene quantum dots (GQDs) in a one-step process. The cytotoxic effects of the free PS and of the corresponding hybrids were compared upon blue (BL) and red-light (RL) exposure on T24 human BC cells. In addition, intracellular reactive oxygen species (ROS) and singlet oxygen generation were measured. TMPyP and Zn-TMPyP showed higher efficiency under BL (IC: 0.42 and 0.22 μm, respectively), while P1-C was more active under RL (IC: 0.14 μm). In general, these PS could induce apoptotic cell death through lysosomes damage. The in vitro photosensitizing activity of the PS was not compromised after their immobilization onto graphene-based nanomaterials, with Zn-TMPyP@GQDs being the most promising hybrid system under RL (IC: 0.37 μg/mL). Overall, our data confirm that GO and GQDs may represent valid platforms for PS delivery, without altering their performance for PDT on BC cells.
开发用于膀胱癌（BC）治疗的新型光动力疗法（PDT）药物对于预防其复发以及向更具侵袭性的形式发展至关重要。在此，三种不同的卟啉类光敏剂（PS）（四甲基吡啶卟啉（TMPyP）、锌-四甲基吡啶卟啉（Zn-TMPyP）和P1-C）通过一步法非共价负载到氧化石墨烯（GO）或石墨烯量子点（GQDs）上。比较了游离PS及其相应复合物在蓝光（BL）和红光（RL）照射下对T24人膀胱癌细胞的细胞毒性作用。此外，还测量了细胞内活性氧（ROS）和单线态氧的产生。TMPyP和Zn-TMPyP在蓝光下表现出更高的效率（IC50分别为0.42和0.22 μM），而P1-C在红光下更具活性（IC50为0.14 μM）。一般来说，这些PS可通过溶酶体损伤诱导凋亡性细胞死亡。PS固定到基于石墨烯的纳米材料上后，其体外光敏活性并未受损，其中锌-四甲基吡啶卟啉@石墨烯量子点（Zn-TMPyP@GQDs）是在红光下最有前景的复合体系（IC50为0.37 μg/mL）。总体而言，我们的数据证实，GO和GQDs可能是PS递送的有效平台，且不会改变它们对膀胱癌细胞进行光动力疗法的性能。
