去势抵抗性前列腺癌（CRPC）严重影响男性患者的生命健康，因缺乏有效治疗手段，导致患者预后不佳。近年来，基于光动力疗法（PDT）的多功能纳米材料的发展为CRPC的治疗提供了希望，但受限于激发光人体穿透性不佳、实体瘤乏氧及缺乏精准影像学方法介导等问题。鉴于此，拟使用人体穿透性佳的X线作为激发光进行PDT，突破激发光人体穿透性不佳的实际问题，还可实现同时放疗。在申请人前期基础上，合成可被X线激发发光的介孔二氧化硅包裹长余辉纳米颗粒（ZGOCS@MSNs），表面偶联可用于MRI成像及改善乏氧的超小MnFe2O4纳米颗粒，负载光敏剂Ce6及使用Chelator-free法标记89Zr，复合成新型多功能纳米颗粒；优化其诊疗参数，在分子、细胞及体内三个层次的研究中，验证其在PET/MRI多模态影像介导PDT协同放疗、改善乏氧增敏治疗CRPC中的作用。本项目的完成将为CRPC的治疗提供新的有效治疗手段。

Castration-resistant prostate cancer (CRPC) seriously affects the health of male patients, the prognosis remains poor for lack of effective treatment modalities. In recent years, the development of photodynamic therapy (PDT) based multifunctional nanomaterials has provided potential for effective treatment of CRPC. However, it is limited by the poor penetration of exciting luminescence to human tissues, the hypoxia of solid tumors and the lack of precise imaging guided therapy. In view of this, we intend to use X-ray, with high human penetration ability, as the exciting light source for PDT, overcoming the actual problem with poor penetrability of exciting light, and also achieving synergistic therapy with radiotherapy. Based on our previous work, we intend to synthesize mesoporous silica coated afterglow luminescence nanoparticles, which can be illumined by X-ray excitation, coupling ultrasmall MnFe2O4 nanoparticles (3nm) on its surface, and labeled with 89Zr using Chelator-free method, loading photosensitizer Ce6 in mesoporous, to form a new multifunctional nanoparticles. Then we optimize its diagnosis and treatment parameters , verify the abilities of PET/MRI multimodal imaging guided, synergistc therapy of PDT combined with radiotherapy, and improve hypoxia of tumor tissue. With this all-in-one multifunctional nanoparticles, we could provide a new and effective method to treat castration-resistant prostate cancer