基于介孔SiO2纳米诊疗剂的肿瘤靶向超声-荧光双模态成像及光热治疗

Nanotheranostics are develped to have dual capabilities for diagnosis and treatment. The nano scale characteristic enables it to pass through the capillary gap and diffuse into interstitial space, thus it can directly attach to the tumor cells. Our study team has fabricated several mesoporous SiO2 based nanatheranostics in the earlier stage, which have the characteristics of near infrare ray (NIR) imaging,MRI, and coordinated effect of thermal therapy and chemotherapy.We also have loaded liquid perfluorocarbon in the inner cavity of the mesoporous nanoparticles, which is able to develop vapouration under high intensity focused ultrasound; thus simultaneous ultrasound imaging and thermal therapy is achieved.On the basis of that, we aim to develop a tumor targeted novel nanotheranostic using the materials such as mesoporous SiO2,quantum dot CdTe,gold nanoparticle,liquid perfluorocarbon, and follic acid.The ultimate goal is to achieve dual mode imaging of ultrasound and fluorescence and photothermal therapy.The dual imaging mode will have both high sensitivity and high resolution in early detection of tumor and the therapy is characterized by accurate targeting to tumor at an early stage.This project will analyze the influence of various parameters on the hole size, wall thickness, and diffusing feature of the nanotheranostics, the imaging effect of ultrasound-fluorescence mode, as well as the photothermal effect. The targeting ability and the biocompatibility of the nanotheranostic will be evaluated. The project will also evaluate the ultrasound/fluorescence tumor imaging effect and the tumor suppression effect of photothermal therapy. Finally, the mechanism of ultrasound/fluorescence bimodal molecular imaging and the photothermal therapy will be explored. The project will provide a new mode for early diagnosis and early therapy for tumor.

纳米诊疗剂兼具诊断和治疗双重特性，能通过肿瘤血管间隙直接作用于肿瘤细胞。项目组前期成功合成了多种介孔硅基纳米诊疗剂，具备近红外光成像、MRI成像、热/化疗协同治疗等特性；并在介孔纳米结构内包载液态氟碳，HIFU作用下产生液-气相变，成功实现了超声显像和热疗。在此基础上，我们提出以介孔硅纳米粒子、CdTe量子点、金纳米、液态氟碳、叶酸等为材料，构建一种肿瘤靶向新型纳米诊疗剂，最终实现超声-荧光双模态分子成像和光热治疗。据此获得一种兼具高灵敏度和高分辨率的肿瘤早期检测方法和早期靶向治疗方法。项目将分析各实验参数对纳米诊疗剂孔径、壁厚、分散性、近红外光下超声/荧光成像效果、光热效应的影响；检测新型纳米诊疗剂的靶向性，考察其生物相容性；观察肿瘤超声/荧光成像效果及光热效应的抑瘤效果；并探讨新型纳米诊疗剂的超声/荧光分子成像和光热治疗机制。本项目将为肿瘤疾病的早期诊断和早期治疗提供一种新的模式。

肿瘤的精确诊断和高效治疗一直是肿瘤诊治中的难题。随着纳米技术的发展，纳米诊疗这一概念已经得到越来越广泛的关注。该课题以恶性肿瘤为研究对象，围绕肿瘤的多模式诊断和影像导航的治疗开展了一系列研究工作，构建多种多模式探针、物理治疗增效剂以及建立多种肿瘤富集方法或策略，如通过结构优化和功能设计的策略构建多模式成像以及内、外源刺激响应型多模式成像探针；构建光热、高强度聚焦超声、射频等物理治疗方式联合化疗实现协同治疗肿瘤的多功能纳米诊疗剂；建立肿瘤超声增强渗透性和主动靶向结合的“接力靶向”、频增强渗透性和主动靶向结合的协同靶向以及表面电荷改性增强肿瘤富集的新型富集策略。通过各种表征、测试手段评价他们的肿瘤中富集效果以及增强诊疗效果和机制，为肿瘤诊治提供了一个新的发展方向，同时也为癌症的综合诊治提供新的思路。