Arterial Embolization Hyperthermia Using As(2)O(3) Nanoparticles in VX(2) Carcinoma–Induced Liver Tumors

BACKGROUND: Combination therapy for arterial embolization hyperthermia (AEH) with arsenic trioxide (As(2)O(3)) nanoparticles (ATONs) is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As(2)O(3) nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee. METHODOLOGY/PRINCIPAL FINDINGS: In total, 60 VX(2) liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group) and received AEH with ATONs (Group 1), hepatic arterial embolization with ATONs (Group 2), lipiodol (Group 3), or saline (Group 4), on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C) was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs). Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups. CONCLUSIONS: ATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis.