Ding Jianan, Mao Qiulian, Zhao Meng, Gao Yinjia, Wang Anna, Ye Shuyue, Wang Xiaoyan, Xie Wei, Shi Haibin
State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, P. R. China.
Nanoscale. 2020 Nov 26;12(45):22963-22969. doi: 10.1039/d0nr06440h.
Radiotherapy (RT) has become one of the most widely used treatments for malignant tumors in clinics. Developing a novel radiosensitizer for the integration of precise diagnosis and effective radiotherapy against hypoxic tumors is desirable but remains a great challenge. Herein, protein sulfenic acid reactive gold nanoparticles as effective radiosensitizers were for the first time reported for enhanced X-ray computed tomography (CT) imaging and radiotherapy of tumors in vivo. The gold nanoparticles were decorated with biocompatible poly(ethylene glycol), folic acid (FA), and sulfenic acid reactive groups 1,3-cyclohexanedione (CHD). Such a nanostructure enables on-site immobilization within tumors under oxidative stress through the specific reaction between CHD and endogenous protein sulfenic acids resulting in enhanced accumulation and retention of gold nanoparticles within tumors, which remarkably improves the sensitivity of CT imaging and the radiotherapeutic efficacy of tumors in living mice. This study thus is the first to demonstrate that protein sulfenic acid reactive gold nanoparticles with a tumor anchoring function may serve as effective radiosensitizers for clinical X-ray theranostic application in the future.
放射疗法（RT）已成为临床上治疗恶性肿瘤应用最为广泛的方法之一。开发一种新型放射增敏剂，用于对缺氧肿瘤进行精确诊断与有效放射治疗，这一想法虽好，但仍是一项巨大挑战。在此，首次报道了蛋白质亚磺酸反应性金纳米颗粒作为有效的放射增敏剂，用于增强体内肿瘤的X射线计算机断层扫描（CT）成像及放射治疗。金纳米颗粒用生物相容性聚乙二醇、叶酸（FA）和亚磺酸反应基团1,3 - 环己二酮（CHD）进行修饰。这种纳米结构能够通过CHD与内源性蛋白质亚磺酸之间的特异性反应，在氧化应激下于肿瘤内原位固定，从而增强金纳米颗粒在肿瘤内的积累和滞留，显著提高活体小鼠CT成像的灵敏度以及肿瘤的放射治疗效果。因此，本研究首次证明具有肿瘤锚定功能的蛋白质亚磺酸反应性金纳米颗粒未来可能成为临床X射线诊疗应用的有效放射增敏剂。
