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Nano-Targeting of Thyrointegrin αvβ3 Receptor in Solid Tumors and Impact on Radiosensitization
Radiation Research ( IF 2.5 ) Pub Date : 2021-07-14 , DOI: 10.1667/rade-21-00031.1
Thangirala Sudha 1 , Mahboob Ur Rehman 2 , Noureldien H E Darwish 1, 3 , Melis Debreli Coskun 1 , Jahangir A Satti 4 , Paul J Davis 1, 5 , Shaker A Mousa 1
Affiliation  

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.



中文翻译:


实体瘤中甲状腺整合素 αvβ3 受体的纳米靶向及其对放射增敏的影响



四碘甲状腺乙酸是甲状腺整合素 αvβ3 的配体,甲状腺整合素 αvβ3 是一种在各种实体瘤和周围新生血管区域中高表达的蛋白质。其纳米衍生物Nano-diamino-tetrac (NDAT)在临床前模型中具有抗癌特性,增强放射敏感性,并在X射线照射后在体外抑制癌细胞生长。本研究使用一种在无菌条件下向肿瘤提供准确放射剂量的新型实验系统,确定了 NDAT 对无胸腺小鼠 SUIT-2 胰腺癌和 H1299 非小细胞肺癌异种移植物的放射增敏作用,以进行肿瘤靶向放射。在这项工作中,低熔点利波维茨合金被用来屏蔽正常器官并允许精确的肿瘤靶向照射。在三周的时间内,带有 SUIT-2 异种移植物的小鼠每天接受不同剂量(0、1、3 或 10 毫克/公斤体重)的 NDAT 治疗和肿瘤靶向照射(1 或 5 Gy)。对带有 SUIT-2 异种移植物的小鼠进行了 30 Gy 测试剂量的验证,与未照射的肿瘤重量相比,肿瘤重量减少了 80% 以上。这项工作的结果表明,NDAT 在降低肿瘤生长和活力方面具有剂量依赖性的放射增敏作用。在接受 5 Gy 肿瘤靶向照射的 H1299 异种移植小鼠中观察到 NDAT(1 毫克/千克体重)的抗癌作用增强,与未照射的肿瘤相比,肿瘤重量减轻,坏死增加。该技术通过新的屏蔽方法证明了精确的肿瘤靶向照射,并结合甲状腺整合素拮抗剂NDAT治疗,在胰腺癌和非小细胞肺癌中显示出抗癌功效。

更新日期:2021-07-14
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