Nano-Targeting of Thyrointegrin αvβ3 Receptor in Solid Tumors and Impact on Radiosensitization.

Abstract

Tetraiodothyroacetic acid is a ligand of thyrointegrin αvβ3, a protein that is highly expressed in various solid tumors and surrounding neovascular regions. Its nano derivative, Nano-diamino-tetrac (NDAT), has anticancer properties in preclinical models, enhances radiosensitivity, and inhibits cancer cell growth in vitro after X-ray irradiation. Using a novel experimental system developed to deliver accurate radiation dose to tumors under sterile conditions, this study establishes NDAT's radiosensitizing effect in SUIT-2 pancreatic cancer and H1299 non-small cell lung carcinoma xenografts in athymic mice for tumor-targeted radiation. In this work, low-melting-point Lipowitz alloy was used to shield normal organs and allow accurate tumor-targeted irradiation. Over a three-week period, mice with SUIT-2 xenografts received daily NDAT treatment at different doses (0, 1, 3, or 10 mg/kg body weight) and tumor-targeted irradiation (1 or 5 Gy). Validation was performed with a test dose of 30 Gy to mice bearing SUIT-2 xenografts and resulted in more than 80% reduction in tumor weight, compared to nonirradiated tumor weight. The results of this work showed that NDAT had a radiosensitizing effect in a dose-dependent manner in decreasing tumor growth and viability. An enhanced anticancer effect of NDAT (1 mg/kg body weight) was observed in mice with H1299 xenografts receiving 5 Gy tumor-targeted irradiation, indicated by decreased tumor weight and increased necrosis, compared to nonirradiated tumors. This technique demonstrated accurate tumor-targeted irradiation with new shielding methodology, and combined with thyrointegrin antagonist NDAT treatment, showed anticancer efficacy in pancreatic cancer and non-small cell lung carcinoma.