Biological effects of irradiating hepatocellular carcinoma cells by internal exposure with 125I-labeled 5-iodo-2'-deoxyuridine-chitosan drug loading nanoparticles

Cancer Biother Radiopharm. 2014 Nov;29(9):395-402. doi: 10.1089/cbr.2014.1693.

Abstract

In this study, the authors evaluate the biological effects of irradiation of hepatocellular carcinoma cells by internal exposure with (125)I-labeled 5-iodo-2'-deoxyuridine ((125)I-UdR)-chitosan drug loading nanoparticles ((125)I-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 (125)I-UdR-CS-DLN for 30 minutes. Survival of HepG2 cells was significantly lower at (125)I-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, (125)I-UdR-CS-DLN induced a higher level of DNA double-strand breaks than (125)I-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 (125)I-UdR-CS-DLN induced significant cell apoptosis in rabbit hepatocellular tumors in situ than (125)I-UdR infusion at the same dose. In conclusion, hepatocellular carcinoma cells were significantly irradiated with (125)I-UdR-CS-DLN compared with (125)I-UdR, and (125)I-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.

Keywords: 125I-UdR-CS-DLN; biological effects; liver cancer; nanoparticles; passive targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / radiotherapy*
  • Chitosan / administration & dosage*
  • Chitosan / pharmacokinetics
  • DNA Damage
  • DNA Repair
  • Hep G2 Cells
  • Humans
  • Idoxuridine / administration & dosage*
  • Idoxuridine / pharmacokinetics
  • Iodine Radioisotopes / administration & dosage*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / radiotherapy*
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / radiotherapy
  • Male
  • Nanoparticles / administration & dosage*
  • Rabbits
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / pharmacokinetics

Substances

  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Chitosan
  • Idoxuridine