设计介孔二氧化钛和上转换纳米材料修饰的中空金纳米球用于诊疗一体化研究

Nanotheranostic systems are efficient path to the early diagnosis and therapy of cancer due to their tracking the treatments in real time and governing the therapeutic process accurately in favor of regulating therapeutic strategies and prognosis guarantee for patients. Upconversion fluorescence nanomaterials (UC) and mesoporous titanium dioxide (MT) and gold nanoshells (ASs) have been demonstrated able to be used for fluorescence imaging and near infrared laser (NIR)-irradiated photodynamic therapy (PDT), respectively, however, the low performance in the fluorescence intensity and the production of reactive oxidative species (ROS) limits their applications. The present project attempts to design and prepare a novel nanotheranostic system through engraftment of MT and UC on the surface of ASs, significantly enhancing the performance of upconversion fluorescence intensity and NIR-irradiated PDT beyond each individual MT, UC and ASs, feasible for the fluorescence imaging and elimination of tumors in deep tissue. The intensities of UC emission can be enhanced by adjusting the thickness of ASs, then, MT can absorb the UV emission from UC spectrum, prompting the separation of electrons and holes in MT and leading to the production of reactive oxygen species. Meanwhile, based on the electron-hole asymmetric transfer theory, UC adjacent to ASs can provide opportunities for hot electrons to transfer from ASs to UC under radiation of 808 nm laser, prompting the separation of electrons and holes in ASs and leading to the more production of reactive oxygen species. This project will also provide a novel strategy for the design of nanotheranostic systems and be of great significance in the early diagnosis and treatment of cancer.

纳米诊疗一体化系统由于其具有药物载体的靶向运输、病灶成像、药物的可控释放及预后检测等多种功能，成为癌症的早期诊断与治疗的有效途径。上转换纳米材料（UC）、介孔二氧化钛（MT）和中空金纳米球（ASs）已被分别用于荧光成像和光动力治疗（PDT），然而荧光强度弱和活性氧产量低限制了它们的应用。本项目拟设计新型纳米诊疗一体化系统，在ASs表面修饰UC和MT来分别增强单一材料的荧光强度和PDT性能，用于深层组织肿瘤的成像和清除。调节ASs壁厚从而有效增强UC的荧光强度；进而，介孔二氧化钛吸收上转换发射的紫外光使得其电子空穴分离，产生活性氧；同时，依据电子-空穴不对称传递理论，UC的相邻存在使得ASs在808nm照射下产生的热电子有机会流向UC，促进电子和空穴在ASs上的分离，利于更多活性氧的产生。这一项目为纳米诊疗一体化系统的设计提供了崭新的思路，对癌症的早期诊断和治疗有着重要意义。

纳米诊疗一体化系统由于其具有药物载体的靶向运输、病灶成像、药物的可控释放及预后检测等多种功能，成为癌症的早期诊断与治疗的有效途径。上转换纳米材料（UC）、介孔二氧化钛（MT）和中空金纳米球（ASs）已被分别用于荧光成像和光动力治疗（PDT），然而荧光强度弱和活性氧产量低限制了它们的应用。我们首先按照研究计划合成了介孔二氧化钛和上转换纳米粒子修饰的中空金纳米球，但是发现其产生活性氧的能力并没有预期好，由于介孔二氧化钛的包覆，上转换的荧光成像能力也被减弱。于是，我们开发了可实现近红外光激发的介孔黑二氧化钛纳米平台，而后负载上转换纳米粒子、小分子探针等功能性材料，利用黑二氧化钛的导带价带与小分子探针的HOMO、LUMO之间存在能级交错匹配，实现电子空穴的有效分离，从而最大化产生活性氧物种，完成肿瘤的治疗与清除。该项目不仅开发了新型纳米诊疗平台，还为癌症的早期诊断和治疗提供了有利的研究基础和材料保障。