Application of temperature-sensitive liquid embolic agent loaded with oxaliplatin in the TACE procedure for rabbit VX2 gastric cancer

Drug Deliv Transl Res. 2024 Mar;14(3):705-717. doi: 10.1007/s13346-023-01425-5. Epub 2023 Sep 5.

Abstract

As a promising drug delivery system, the temperature-sensitive liquid embolic agent (TempSLE) has yet to be reported in animal experiments in treating gastric cancer. We observed and compared computed tomography (CT) imaging changes, tumor volume, HE staining, and immunohistochemistry after transcatheter arterial chemoembolization (TACE) treatment in rabbit VX2 gastric cancer models to clarify the effectiveness of TempSLE loaded with oxaliplatin (TempSLE/Oxa) in treating gastric cancer. One milliliter TempSLE can be loaded with 20 mg oxaliplatin. The accumulative drug release rate at 30 min was 38.76%, and after 24 h, it reached more than 90%. CT examination 1 week after TACE revealed that the TempSLE/Oxa group presents unenhanced hypodense necrotic foci, the iodinated oil loaded with oxaliplatin (Ioil/Oxa) group presents shrinking tumors but still visible speckled foci of enhancement, and the normal saline (NS) group presents heterogeneous enhancement with larger tumors than before. In the postoperative autopsy of TACE, the tumor volumes of TempSLE/Oxa, Ioil/Oxa, and NS groups were 0.15 ± 0.06 cm3, 0.37 ± 0.11 cm3, and 1.19 ± 0.16 cm3, respectively, all of which were statistically different. The positive vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression percentages in the TempSLE/Oxa, Ioil/Oxa, and NS groups were statistically different and lowest in the TempSLE/Oxa group. In conclusion, the TempSLE can load a high dose of oxaliplatin to meet the demand of clinical applications. TempSLE/Oxa could effectively inhibit tumor cell proliferation and angiogenesis. This study provides experimental evidence for the further clinical application of the TempSLE/Oxa.

Keywords: Oxaliplatin; Temperature-sensitive liquid embolic agent; Transcatheter arterial chemoembolization; VX2 gastric cancer.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular*
  • Chemoembolization, Therapeutic* / methods
  • Liver Neoplasms* / therapy
  • Oxaliplatin
  • Rabbits
  • Stomach Neoplasms* / drug therapy
  • Temperature
  • Vascular Endothelial Growth Factor A

Substances

  • Oxaliplatin
  • Vascular Endothelial Growth Factor A