State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1843-1851. doi: 10.1021/acsabm.0c01537. Epub 2021 Jan 27.
Nanoradiosensitizers containing high-Z elements hold great potential in radiotherapy owing to the increasing energy deposition effect on X-ray irradiation. However, their potential clinical application is limited by the irradiation damage in nontarget tissues surrounding the tumor site, as well as the safety concerns for nanomaterials. Our findings demonstrate that pharmacological ascorbate displays a synergistic radiosensitizing effect in combination with nanoradiosensitizers. By engineering the Au@Pd core-shell nanostructures and precisely regulating their shell thickness, the obtained Au@Pd nanomaterials exhibit excellent ascorbate oxidase-like activity. Along with the accelerating generation of HO, pharmacological ascorbate significantly enhances the radiosensitizing effect of Au@Pd-PEG nanoparticles on both cancer cells and solid tumor. Interestingly, pharmacological ascorbate effectively protects normal tissues from X-ray-induced injury. The present work demonstrates that pharmacological ascorbate is an ideal agent for selectively improving the radiosensitizing effect of nanomaterials, providing a promising strategy to facilitate the clinical translation of nanoradiosensitizers.
含高原子序数元素的纳米增敏剂在放射治疗中具有很大的潜力，因为它们在 X 射线照射下会增加能量沉积效应。然而，它们在肿瘤部位周围非靶组织中的辐照损伤以及对纳米材料的安全性问题限制了其潜在的临床应用。我们的研究结果表明，药理剂量的抗坏血酸与纳米增敏剂联合使用具有协同放射增敏作用。通过工程化 Au@Pd 核壳纳米结构并精确调节其壳层厚度，所获得的 Au@Pd 纳米材料表现出优异的抗坏血酸氧化酶样活性。随着 HO 的加速生成，药理剂量的抗坏血酸显著增强了 Au@Pd-PEG 纳米颗粒对癌细胞和实体瘤的放射增敏作用。有趣的是，药理剂量的抗坏血酸有效地保护正常组织免受 X 射线诱导的损伤。本研究表明，药理剂量的抗坏血酸是一种理想的选择性提高纳米材料放射增敏作用的试剂，为促进纳米增敏剂的临床转化提供了一种有前景的策略。
