多肽靶向纳米孔核壳上转换发光体系的构筑及诊疗一体化

The early diagnosis and therapy of cancer is an urgent issue for human beings. This project aims at preparing a series of peptide targeted nanopore core-shell upconversion luminescent nanomaterials for cancer diagnosis and photodynamic therapy. This high efficiency targeted cancer diagnosis and treatment integration system tends to combine upconversion optical sensors and nanopore photosensitizer polymer shell, which their individual characters can be well conducted. To improve the performance of this system, we choose excellent photostability and high singlet oxygen quantum yield photosensitizers such as Ruthenium complex, Iridium complex and BODIPY as nanopore polymer shell; use LHRH with strong tumor-specific identification ability as the targeted molecular to integrate the diagnosis and photodynamic therapy of cancer. The project will pay special attention to the factors affecting the therapy efficiency such as type of photosensitizer, particle size, radiation intensity and targeted molecular distribution in vivo, to obtain a cancer diagnosis and photodynamic therapy system with excellent therapeutic effect and some meaningful targeting data. These results will provide theoretical and experimental guidance for the accurate and rapid detection and treatment of cancer, promote the application and development of photodynamic therapy system.

癌细胞的早期诊断和靶向治疗是人类面临的重大科学问题。本项目拟以对癌细胞具强特异性识别能力的促黄体激素释放激素(LHRH)多肽受体为靶向，以上转换发光纳米粒子为核心，通过聚合反应将选定的有望高效产生单线态氧(1O2)的光敏剂分子直接包覆在上转换粒子表面多孔聚合物层内，构筑上转换发光诊断-光动力学治疗的高效靶向诊疗一体化体系。考察以不同光敏剂如钌配合物、铱配合物和BODIPY等作为单体在体系中上转换光激发下产生1O2的效率，通过LHRH多肽精确识别癌细胞，确保所产生的1O2能够快速到达靶点杀灭癌细胞。通过本项目的实施以期获得一种近红外光激发下对癌症特异性检测效果好、光动力学治疗效果佳的诊疗一体化体系，为癌症的精准快速检测和治疗提供理论依据和实验参考，推动靶向上转换光动力学治疗体系的发展。

癌细胞的早期诊断和靶向治疗是人类面临的重大科学问题。我们以上转换发光纳米粒子为核心，制备出多孔材料包覆的 β-NaYF4-纳米材料，所制备的纳米孔材料具有高的比表面积及大的孔体积，有利于提高对光敏剂分子的吸附。装载光敏剂分子后，该复合材料在近红外光照射下发出的绿色上转换发光并进一步激发了光敏剂分子，激发态的光敏剂分子可以与周围的氧气分子相互作用，生成对癌细胞具有杀伤力的单线态氧。制备出具有靶向运输和光控释放性质的多功能多孔纳米复合材料。利用药物模型探讨了多功能纳米复合材料作为药物载体的可行性。在光照射下可以触发复合材料将负载的药物模型释放出来. 通过光刺激的“开关”实现了对药物模型的精确可控释放。利用体外实验研究了药物的光控释放行为和靶向运输功能。利用MOF材料和光敏剂钌配合物的电荷属性相反，通过离子交换法构筑了具有双光子上转换激发发射能力的复合材料体系：MOF-Ru。实验结果表明该材料体系提高了原有钌配合物光敏剂分子在近红外光波段（生物组织光学窗口）的双光子上转换发光效率，进而提升了光敏剂在光催化下产生单线态氧的能力。光学实验表明纳米粒子被细胞有效摄取，MTT实验表明光动力学治疗降低了癌细胞的活性。以上结果为上转换发光纳米粒子/含光敏剂多孔材料在生物医学领域的应用提供了有益的参考。