降期治疗是重建多数中晚期肝癌患者手术切除机会的有效策略。经肝动脉放射栓塞（TARE）治疗是最佳的降期手段之一。当前商业化90Y微球在TARE治疗中存在核素易浸出，非可视化等缺点，导致其在安全性与精准度上存在不足。本项目拟将90Y标记到NIR-Ⅱ纳米探针上，再将标记的探针包载于聚苯乙烯（PS）微球中，制备90Y-NIR-Ⅱ-PS放射栓塞微球。该微球利用90Y与双磷酸螯合可实现90Y稳定标记，有效降低核素浸出造成的放射毒性。微球集成纳米探针的X射线造影功能，可实现介入栓塞可视化，大大提高TARE治疗精度。而其集成的MRI，CT对比剂功能，使栓塞效果和肿瘤降期疗效可通过MRI、CT评价。此外，在降期后，其集成的NIR-Ⅱ成像功能，使肿瘤精准切除可在NIR-Ⅱ荧光导航下进行。最后，该微球的治疗效能将通过兔VX2肝癌模型进行评估验证。本项目的顺利实施将为中晚期肝癌更安全、精准地治疗提供新的参考。

Downstaging treatment is an effective strategy in rebuilding surgical resection opportunity for most patients with moderate or advanced hepatocellular carcinoma. Transcatheter radioembolization (TARE) has been proved to be one of the most suitable downstaging way. But, the current available commercial 90Y microspheres in TARE treatment still remaining many defects that deserves more serious attentions, such as nuclide leaching and non-visualization, which gives rise to tremendous risk of biosafety and accuracy of TARE treatment. The current proposal aims to construct a new type of multifunctional 90Y-NIR-Ⅱ-PS radiation embolization microspheres for TARE treatment by labeling 90Y to the NIR-Ⅱ nanoprobe and then encapsulating it into the polystyrene (PS) microsphere. The conceived microsphere can chelate 90Y stably with bisphosphate group, thus significantly reducing the radionuclide leaching and the subsequent radiotoxicity. The integrated X-ray angiography function of the nanoprobe into the microsphere endows accurate interventional embolization of microsphere, thereby enhancing the precise of TARE downstaging treatment. Meanwhile, the integrated MRI and CT contrast agent functions leading it is visible to assess the effects of interventional embolism and tumor downstaging using MRI and CT imaging. In addition, the integrated NIR-Ⅱ imaging function makes the precise resection of tumors guided by NIR-Ⅱ fluorescence after downstaging becomes feasible. More importantly, the real treatment performance of the microsphere will be studied using the rabbit VX2 hepatocellular carcinoma model. The successful completion of this project should provide a new sample for safer and more accurate treatment of moderate or advanced hepatocellular carcinoma.