School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin, China.
Chem Biol Interact. 2012 Jan 5;195(1):86-94. doi: 10.1016/j.cbi.2011.11.003. Epub 2011 Nov 15.
Photodynamic therapy is an emerging, externally activatable, treatment modality for various diseases, especially for cancer therapy. The photodynamic activities of tumor targeting water-soluble C(60) derivatives (WSFD) were evaluated on HeLa cells. To overcome the poor solubility, biocompatibility and selectivity of C(60), we modified C(60) with l-phenylalanine, folic acid and l-arginine. Consistent with their photodynamic abilities, WSFD generated the reactive oxygen species after irradiation both in water and in vitro. No dark cytotoxicity was observed using 5μg/mL WSFD during long incubation time. Furthermore, the uptake of WSFD into HeLa cells was much more than normal cells, which indicated the WSFD had selectivity to tumor cells. Investigation of the possible photodynamic activities of WSFD demonstrated that they expressed photokilling activities by raising the level of (1)O(2)/O(2)(-) under visible light irradiation. In parallel, following exposure of cells to WSFD and irradiation, a marked decrease in mitochondrial membrane potential, cell viability, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as increased malondialdehyde (MDA) production were observed. Moreover, WSFD caused significant elevation in caspase-3 activity, and induced apoptotic death. Experiments demonstrated that both chemical properties, such as the chemical structure of adduct and addend numbers, and physical properties, such as degree of aggregation, influenced the ROS-generation abilities, cellular uptake and photodynamic activities of WSFD. The results suggest that WSFD have the potential application in cancer cell inactivation by photodynamic therapy.
光动力疗法是一种新兴的、外部激活的治疗方法，可用于治疗各种疾病，特别是癌症治疗。我们评估了肿瘤靶向水溶性 C(60)衍生物（WSFD）的光动力活性在 HeLa 细胞上的作用。为了克服 C(60)的溶解度差、生物相容性和选择性差的问题，我们用苯丙氨酸、叶酸和精氨酸对 C(60)进行了修饰。与它们的光动力能力一致，WSFD 在光照和体外条件下均能产生活性氧。在长时间孵育过程中，即使使用 5μg/mL 的 WSFD，也没有观察到暗毒性。此外，WSFD 进入 HeLa 细胞的摄取量明显高于正常细胞，这表明 WSFD 对肿瘤细胞具有选择性。对 WSFD 可能的光动力活性的研究表明，它们通过在可见光照射下提高（1）O2/O2-水平来表达光杀伤活性。同时，细胞暴露于 WSFD 和光照后，线粒体膜电位、细胞活力、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）活性明显降低，丙二醛（MDA）生成增加。此外，WSFD 导致 caspase-3 活性显著升高，并诱导细胞凋亡。实验表明，化学性质（如加合物的化学结构和加合数）和物理性质（如聚集程度）都影响了 WSFD 的 ROS 生成能力、细胞摄取和光动力活性。结果表明，WSFD 具有通过光动力疗法使癌细胞失活的潜力。
