硒化物纳米粒子放疗增敏与放疗防护机制研究及其生物安全性评价

In this proposal, we try to develop a new radiosensitizer based on selenide nanoparticles that could not only enhance the radio-therapeutic effects in tumor but also promote radioprotection in normal tissues. For example, in our previous work, we found Bi2Se3 exhibit significantly enhanced free radical generation upon X-ray radiation and remarkable photothermal effects under 808 nm NIR laser irradiation, because of their strong X-ray attenuation ability and high NIR absorption capability. Moreover, these Bi2Se3 nanoparticles are biodegradable. In vivo, part of selenium can be released from NPs and enter the blood circulation system, which can enhance the immunologic function and reduce the side-effects of radiation in whole body. We try to systematically investigate this kind of nanoscale radiosensitizer in terms of its radio-enhancement and radioprotection mechanism, biodegradable behavior and biosafety. We will also try to figure out the general rules for reasonable design and fabrication of nanoscale radiosensitizers with better therapeutic effects and reduced side effects in radiotherapy that will extend the application fields of selenide nanoparticles.

本项目以进一步推动纳米材料在放疗增敏中的应用为目标,以提高放疗效果，降低放疗毒副作用为切入点，以硒化物纳米粒子为基础，利用硒化物纳米粒子（如Bi2Se3）X-射线吸收效果好、光热转换效率高及可生物降解的特点，构建新型放疗增敏药物体系，促进胞内自由基生成，提高辐照敏感性，降低毒副作用，改善治疗效果；同时，系统研究这类材料的放疗增敏机制，获取具有一定通用性的纳米材料理化特性（如尺寸、形貌、表面特性、合成方法等）与放疗增敏构效关系规律；探索硒元素对放疗防护的作用，明确硒化物纳米粒子的分解代谢规律，对其生物学效应和毒性进行系统性评价；拓展纳米粒子介导的放疗与热疗,化疗等有机结合，提高放疗敏感性，实现肿瘤的综合治疗；这些工作不仅有助于充分阐释硒化物纳米材料放疗增敏机制，为其在生物领域应用提供依据，同时也有助于进一步理解纳米材料与放疗增敏构效关系，从而改进材料的性能，拓展应用范围，发现新的应用领域。

本项目以进一步推动纳米材料在放疗增敏中的应用为目标,以提高放疗效果，降低放疗毒副作用为切入点，以硒化物纳米粒子为基础，利用硒化物纳米粒子（如Bi2Se3）X-射线吸收效果好、光热转换效率高及可生物降解的特点，构建新型放疗增敏药物体系，促进胞内自由基生成，提高辐照敏感性，降低毒副作用，改善治疗效果；同时，系统研究这类材料的放疗增敏机制，获取具有一定通用性的纳米材料理化特性（如尺寸、形貌、表面特性、合成方法等）与放疗增敏构效关系规律；探索硒元素对放疗防护的作用，明确硒化物纳米粒子的分解代谢规律，对其生物学效应和毒性进行系统性评价；拓展纳米粒子介导的放疗与热疗,化疗等有机结合，提高放疗敏感性，实现肿瘤的综合治疗；这些工作不仅有助于充分阐释硒化物纳米材料放疗增敏机制，为其在生物领域应用提供依据，同时也有助于进一步理解纳米材料与放疗增敏构效关系，从而改进材料的性能，拓展应用范围，发现新的应用领域。