二氧化钛/稀土上转换发光纳米复合材料的合成及其近红外光响应光动力疗法抗肿瘤作用的研究

Photodynamic therapy (PDT) is a novel and effective antitumor treatment method. As low phototoxic photosensitizer, titanium dioxide nanoparticles (TiO2 NPs) have potential application in the inhibition of cancer because of their excellent photocatalytic activity, little noxious and chemical stability. Like other conventional photosensitizers, TiO2 NPs have the two challenges. On one hand, the normal cells can be killed during the inhibition of cancer cells by the PDT due to non-selective of TiO2 NPs. On the other hand, as the excitation source of TiO2 NPs, ultraviolet light shows very limited tissue penetration depth. To resolve these problems, in this project, we will focus on the design and synthesis of UCNPs@TiO2 nanocomposites composed of TiO2 NPs coated up-conversion nanoparticles (UCNPs) with uniform morphology, good dispersion and core-shell structure. Up-conversion luminescent UCNPs@TiO2 can be served as near-infrared light responsive photosensitizer without introducing other photosensitizers in the PDT. UCNPs play two roles. Firstly, UCNPs can convert deeply tissue penetrating near-infrared light to ultraviolet light, and TiO2 NPs on the surface of UCNPs can absorb the ultraviolet light to obtain photocatalytic activity. Secondly, they can serve as imaging contrasts to monitor and track the in vivo delivery and distribution of UCNPs@TiO2 nanocomposites. In addition, the UCNPs@TiO2 nanocomposites are further surface-functionalized by anti carcinoembryonic antigen monoclonal antibody to gain the tumor targeting capacity. Finally, in vitro and in vivo antitumor effect and mechanism of UCNPs@TiO2 by near-infrared light responsive PDT will be investigated in detail.

光动力疗法(PDT)是一种新兴的治疗肿瘤的有效方法。纳米TiO2因具有出色的光催化性能、良好的生物相容性和稳定的化学性质而有望成为有效治疗癌症且毒副反应小的光敏剂。与其它光敏剂一样，TiO2也存在一些问题：一是不具有选择性，光动力抑制肿瘤细胞时正常细胞也会被杀死；二是激发纳米TiO2的紫外光的组织穿透深度较浅。针对这些问题，本项目中我们将合成形貌均匀和分散性好的纳米TiO2包覆上转换发光纳米粒子(UCNPs)的核壳纳米复合材料(UCNPs@TiO2)，构建近红外光响应的TiO2光敏剂。UCNPs具有双重作用，一是将组织穿透深度较深的近红外光转换为紫外光并传递给UCNPs表面的纳米TiO2；二是作为成像试剂监测光敏剂在生物体内的传递和分布情况。经抗癌胚抗原单抗表面修饰后，UCNPs@TiO2能够靶向输送到肿瘤细胞，深入研究UCNPs@TiO2体外/体内的近红外光响应PDT抑制肿瘤效果和机制。

光动力疗法(PDT)是一种新兴的治疗肿瘤的有效方法。纳米TiO2 因具有出色的光催化性能、良好的生物相容性和稳定的化学性质而有望成为有效治疗癌症且毒副反应小的光敏剂。与其它光敏剂一样，TiO2 也存在一些问题：一是不具有选择性，光动力抑制肿瘤细胞时正常细胞也会被杀死；二是激发纳米TiO2 的紫外光的组织穿透深度较浅。针对这些问题，本项目中我们将合成形貌均匀和分散性好的纳米TiO2 包覆上转换发光纳米粒子(UCNPs)的核壳纳米复合材料(UCNPs@TiO2)，构建近红外光响应的TiO2 光敏剂。UCNPs 具有双重作用，一是将组织穿透深度较深的近红外光转换为紫外光并传递给UCNPs 表面的纳米TiO2；二是作为成像试剂监测光敏剂在生物体内的传递和分布情况。经抗癌胚抗原单抗表面修饰后，UCNPs@TiO2 能够靶向输送到肿瘤细胞，深入研究UCNPs@TiO2 体外/体内的近红外光响应PDT抑制肿瘤效果和机制。