THC对脑胶质瘤的放射增敏作用及Tf介导的多功能环境响应递释系统用于同步放化疗的研究

Most glioma not sensitive to radiation or the sensitivity reducing after a period of radiation therapy. The radiosensitizer can improve the efficacy of radiotherapy, and curcumin has been shown to be an effective radiosensitizer. We have found that tetrahydrocurcumin (THC) is the primary metabolite of curcumin in vivo, which suggests that THC may be responsible for the radiosensitization of curcumin. In this study we intend to use two strategies of therapy on glioma as radiosensitization and targeted drug delivery. On one hand, the mechanism of THC on radiosensitization of gliomas will be investigated , which lead to find the efficient and low toxicity radiosensitizer. On the other hand，THC with doxorubicin will be entrapped in PEG-PLGA with sodium bicarbonate (NaHCO3) as gas substances，and the Tf will be modified on the surface of particles.Transferrin receptor express at high levels on the blood-brain barrier and glioma, while the tumor has internal acidic environment. Thus the drug system targeting to glioma by the synergies of receptor-mediated and pH-response, result in accumulation of both drugs in the glioma tissue which benefit for the concurrent chemoradiotherapy.

大多数胶质瘤对放射线不敏感或者放射治疗一段时间后敏感性降低，应用放射增敏剂使得射线对肿瘤的杀伤力增加，可以提高放射治疗的疗效。姜黄素已被证实为一种有效的放疗增敏剂，课题组前期研究发现姜黄素在体内主要以代谢产物四氢姜黄素（Tetrahydrocurcumin，THC）的形式存在，推测后者是姜黄素产生放疗增敏作用的物质基础。本项目拟将放疗增敏和脑胶质瘤靶向给药这两种治疗策略相结合，对THC对脑胶质瘤放疗增敏的作用及其机制进行探讨，为寻找高效、低毒的放射增敏化合物提供实验基础。并将THC与阿霉素包载于载体材料PEG-PLGA中，以碳酸氢钠（NaHCO3）为产气物质，将Tf修饰于粒子的表面，利用血脑屏障及脑胶质瘤表面高水平表达的转铁蛋白受体和脑胶质瘤内部存在的酸性环境，产生受体介导和酸性响应的协同作用，增加两种药物在肿瘤组织的蓄积，用于脑胶质瘤的同步放化疗，为联合治疗提供便利。