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14 July 2021 Nano-Targeting of Thyrointegrin αvβ3 Receptor in Solid Tumors and Impact on Radiosensitization
Thangirala Sudha, Mahboob Ur Rehman, Noureldien H. E. Darwish, Melis Debreli Coskun, Jahangir A. Satti, Paul J. Davis, Shaker A. Mousa
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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.

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Thangirala Sudha, Mahboob Ur Rehman, Noureldien H. E. Darwish, Melis Debreli Coskun, Jahangir A. Satti, Paul J. Davis, and Shaker A. Mousa "Nano-Targeting of Thyrointegrin αvβ3 Receptor in Solid Tumors and Impact on Radiosensitization," Radiation Research 196(4), 375-385, (14 July 2021). https://doi.org/10.1667/RADE-21-00031.1
Received: 24 January 2021; Accepted: 21 June 2021; Published: 14 July 2021
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