Biological Effects of Irradiating Hepatocellular Carcinoma Cells by Internal Exposure with 125I-Labeled 5-Iodo-2′-Deoxyuridine-Chitosan Drug Loading Nanoparticles

摘要

In this study, the authors evaluate the biological effects of irradiation of hepatocellular carcinoma cells by internal exposure with ¹²⁵I-labeled 5-iodo-2′-deoxyuridine (¹²⁵I-UdR)-chitosan drug loading nanoparticles (¹²⁵I-UdR-CS-DLN). The authors observed that accumulation of nanoparticles was significantly (p<0.05) higher in hepatocellular carcinoma cells HepG2 than normal liver cells HL-7702 after treated with ¹²⁵I-UdR-CS-DLN for 30 minutes. Survival of HepG2 cells was significantly lower at ¹²⁵I-UdR-CS-DLN doses higher than 37 kBq/mL (more significant in the G1 phase and G2/M phase) than the HL-7702 cells. In addition, ¹²⁵I-UdR-CS-DLN induced a higher level of DNA double-strand breaks than ¹²⁵I-UdR, and HepG2 cells exhibited a lower level of DNA repair when compared with HL-7702 cells. In vivo animal experiments, TUNEL staining, after targeted treatment, showed that ¹²⁵I-UdR-CS-DLN induced significant cell apoptosis in rabbit hepatocellular tumors in situ than ¹²⁵I-UdR infusion at the same dose. In conclusion, hepatocellular carcinoma cells were significantly irradiated with ¹²⁵I-UdR-CS-DLN compared with ¹²⁵I-UdR, and ¹²⁵I-UdR-CS-DLN irradiation enhanced DNA damage, induced liver cancer cell apoptosis, and prevented DNA damage repair. However, evaluating the extent of damage and organ sparing in vivo should also be considered.