上转换近红外长余辉发光纳米诊疗体系的构建、成像及靶向抗肿瘤研究

Difficulty of early diagnosis and poor efficacy of conventional cancer diagnoise and therapy are two main factors for the high cancer mortality. As a novel anti-cancer modality, near-infrared (NIR) triggered photodynamic therapy (PDT) has gained considerable attention recently. However, the continuous and intense excitation makes itdifficult for completion of the full course of imaging and therapy, especially for the tissues or organs in deep parts of the body in spite of the deeper penetration depth compared with ultra-violet (UV) excitation light. Furthermore, the nuclear targeting is still a challenge. To address all above issues, in this project, we are to design and fabricate silica coated up-conversion persistent luminescent nanoparticles (UCPLNPs) with high dispersity and controllable particle size. After that, the photosensitizers (PSs) molecules and targeted TAT peptide are covalently incorporated into the mesopore of the carrier, resulting in the formation of a novel imaging guided theranostics nanoplatform. The superiority of UCPLNPs is that after ceasing the NIR excitation, the NIR long-persistent emission excited by NIR laser light can guarantee the whole course of imaging and PDT process, which has never been reported so far. Except that, the dispersion of the material in mouse body, the fluorescence imaging and anti-cancer PDT efficacy have been well investigated in vitro and in vivo.

传统的癌症诊疗手段的低疗效及早期诊断困难是造成癌症高死亡率的重要原因。作为一种新型治疗手段，近红外光触发的光动力治疗（PDT）在癌症治疗领域引起广泛的关注，但也存在一些关键问题：需要不间断的持续激发来保障光动力过程的进行。虽然与紫外激发光相比近红外光的组织穿透深度大幅提高，但依然不能完全满足体内深层组织成像和光动力治疗的需要。此外，细胞核靶向传递一直是该领域的难点之一。针对上述问题，本项目拟制备合成一类新型近红外光激发的近红外长余辉纳米发光材料，然后将介孔SiO2包覆其表面制备一种粒径均匀、尺寸可控的纳米载体；优化偶联和修饰方法，将光敏剂分子及核靶向试剂TAT肽修饰到体系的介孔内，构建新型纳米诊疗体系。这种上转换近红外长余辉发光材料的优势在于：激发停止后，长时间持续发射的近红外光能够保证成像和光动力治疗的顺利进行。此外，深入研究材料在活体内分布、荧光成像及体外、体内的光动

传统的癌症诊疗手段的低疗效及早期诊断困难是造成癌症高死亡率的重要原因。作为一种新型治疗手段，近红外光触发的光动力治疗（PDT）在癌症治疗领域引起广泛的关注，但也存在一些关键问题：需要不间断的持续激发来保障光动力过程的进行。虽然与紫外激发光相比近红外光的组织穿透深度大幅提高，但依然不能完全满足体内深层组织成像和光动力治疗的需要。此外，细胞核靶向传递一直是该领域的难点之一。针对上述问题，本项目拟制备合成一类新型近红外光激发的近红外长余辉纳米发光材料，然后将介孔SiO2包覆其表面制备一种粒径均匀、尺寸可控的纳米载体；优化偶联和修饰方法，将光敏剂分子及核靶向试剂TAT肽修饰到体系的介孔内，构建新型纳米诊疗体系。这种上转换近红外长余辉发光材料的优势在于：激发停止后，长时间持续发射的近红外光能够保证成像和光动力治疗的顺利进行。此外，深入研究材料在活体内分布、荧光成像及体外、体内的光动