Cardinali Camila Aparecida Errerias Fernandes, Fabiano de Freitas Camila, Sonchini Gonçalves Renato, Amanda Pedroso de Morais Flavia, Nunes de Lima Martins Juliana, Martins Yandara Akamine, Fernando Comar Jurandir, de Souza Bonfim-Mendonça Patrícia, Tessaro André Luiz, Kimura Elza, Caetano Wilker, Hioka Noboru, Brunaldi Kellen, Ravanelli Maria Ida
Departament of Physiological Sciences, State University of Maringa, Maringa, Parana 87020-900, Brazil.
Department of Chemistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina 88040-380, Brazil.
ACS Omega. 2024 Dec 28;10(1):1100-1109. doi: 10.1021/acsomega.4c08553. eCollection 2025 Jan 14.
Glioblastoma Multiforme (GBM) is one of the most aggressive types of brain tumor. GBM can modulate glutathione (GSH) levels and regulate cellular redox state, which can explain its high resistance to chemotherapeutic agents. Photodynamic therapy (PDT) is a selective, nontoxic, and minimally invasive treatment approved for many types of cancer. PDT leads to cell death mainly by promoting the generation of reactive oxygen species (ROS). Thus, in the current study, PDT with the photosensitizer hypericin (Hyp), formulated in mixed 1,2-dipalmitoyl--glycero-3-phosphocholine (DPPC)/biotinylated-pluronic F127 (F127-B) liposomes, in combination with the GSH synthesis inhibitor buthionine sulfoximine (BSO) were tested against T98G cell line of human glioblastoma. The mixed liposome was effective in delivering Hyp to the cells, leading to a dose relationship between Hyp and ROS levels. BSO potentiated Hyp cell uptake, decreased GSH levels regardless of Hyp concentration, and intensified ROS generation for 1.00 and 5.00 μmol L Hyp. Nonetheless, cell death was more pronounced in the groups not treated with BSO, indicating that reduced GSH levels are not a decisive factor in achieving the PDT effects of Hyp. In conclusion, the mixed DPPC/F127-B liposomes were effective as a delivery system for Hyp. However, the combination of BSO and Hyp was not capable of optimizing PDT against T98G cells.
多形性胶质母细胞瘤(GBM)是最具侵袭性的脑肿瘤类型之一。GBM可调节谷胱甘肽(GSH)水平并调控细胞氧化还原状态,这可以解释其对化疗药物的高度耐药性。光动力疗法(PDT)是一种已被批准用于多种癌症的选择性、无毒且微创的治疗方法。PDT主要通过促进活性氧(ROS)的生成导致细胞死亡。因此,在本研究中,测试了将金丝桃素(Hyp)包裹于1,2 - 二棕榈酰 - sn -甘油 - 3 - 磷酸胆碱(DPPC)/生物素化普朗尼克F127(F127 - B)混合脂质体中,并与GSH合成抑制剂丁硫氨酸亚砜胺(BSO)联合使用,对人胶质母细胞瘤T98G细胞系的作用。混合脂质体能够有效地将Hyp递送至细胞,导致Hyp与ROS水平之间存在剂量关系。BSO增强了Hyp的细胞摄取,无论Hyp浓度如何均降低了GSH水平,并在Hyp浓度为1.00和5.00 μmol/L时增强了ROS的生成。然而,未用BSO处理的组细胞死亡更为明显,这表明GSH水平降低并非实现Hyp光动力治疗效果的决定性因素。总之,DPPC/F127 - B混合脂质体作为Hyp的递送系统是有效的。然而,BSO与Hyp的联合并不能优化对T98G细胞的光动力治疗。