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

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

Chen Yang  1 , Ran Zhu, Jianmei Wan, Bo Jiang, Dayong Zhou, Miaoli Song, Fenju Liu
Affiliations

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

Chen Yang et al. Cancer Biother Radiopharm. 2014 Nov.

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.

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Figures

<b>FIG. 1.</b>
FIG. 1.
Fluorescence distribution after fluorescein isothiocyanate-labeled chitosan nanoparticle (FITC-CS-NP) treatment in HepG2 and HL-7702 cells under a confocal microscope.
<b>FIG. 2.</b>
FIG. 2.
Effect of 125I-labeled 5-iodo-2′-deoxyuridine-chitosan drug loading nanoparticles (125I-UdR-CS-DLN) on HL-7702 and HepG2 cell survival. HL-7702 and HepG2 cells treated with different doses of 125I-UdR or 125I-UdR-CS-DLN for 24 and 48 hours, and the cell survival rate was assessed by the MTT assay (*p<0.05, **p<0.01).
<b>FIG. 3.</b>
FIG. 3.
Effect of 125I-UdR-CS-DLN on HL-7702 and HepG2 cell cycle. HL-7702 and HepG2 cells treated with 125I-UdR or 125I-UdR-CS-DLN (37 kBq/mL) for 48 hours, Cell division was analyzed by a flow cytometry (**p<0.01). (A) HL-7702 cells. (B) HepG2 cells.
<b>FIG. 4.</b>
FIG. 4.
Comet tailing phenomenon at 24 hours postirradiation.
<b>FIG. 5.</b>
FIG. 5.
Gross pathology—digital subtraction angiography and single-photon emission computed tomography (SPECT) imaging of rabbit liver VX2 tumor model. (A) Left liver lobe with 9.2±1.3 mm average lesion size. (B) Left hepatic artery superselected by Seldinger microcatheter. (C) SPECT imaging at 24 hours postirradiation. (D) 125I-UdR-treated rabbits with weak radioactivity. (E) TUNEL staining of rabbit liver VX2 tumor at 48 hours postinfusion of 125I-UdR-CS-DLN, 125I-UdR, and sham operation group. White arrows indicate location and size of the tumor.
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