基于超分子主客体组装构建的核-壳结构树状大分子纳米平台用于肿瘤靶向的多模态成像与协同治疗

构建具有多模态成像功能的纳米平台用于化疗药物与siRNA的高效、靶向输送，有望通过两者的协同作用提高肿瘤治疗效果、降低毒副作用，并追踪药物影像、监测疗效以实现癌症的个体化精准治疗。本项目利用纳米技术合成表面分别修饰β-环糊精、金刚烷与聚乙二醇-RGD多肽的功能化聚酰胺胺树状大分子组件，以简便、高效的超分子化学技术可控组装成为靶向整合素αvβ3高表达肿瘤的核-壳结构树状大分子纳米平台，利用其内部疏水性空腔负载抗肿瘤药物、表面负载治疗siRNA实现基因治疗与化学药物的联合治疗，并利用树状大分子组件中的金纳米颗粒、核医学造影元素进行纳米平台在体内的CT与SPECT成像，实现对纳米平台在体内输送行为以及治疗效果的实时监测。本研究构建的核壳结构树状大分纳米平台子不仅有望用于肿瘤的可视化、个体化精准治疗，还为多功能纳米平台的构建提供了新的思路。

A multifunctional nanocarrier platform which is capable of combining targeted delivery of chemotherapeutic agents and siRNA together with multimodal imaging agent will enable improved anti-cancer efficacy, lower toxic side effects of anti-cancer drugs and in the meantime individualized high potency therapy by the real time in vivo monitoring of targeted tumors. In this project, functionalized dendrimers as the macromolecular building blocks for the construction of a nanocarrier platform which can target tumors overexpressing integrin αvβ3 are designed and developed by surface modification of PAMAM dendrimers with β-cyclodextrin, adamantine, and PEG-RGD polypeptide respectively. The hydrophobic interior cavity of the dendrimers is used to load anticancer drug, while the surface is loaded with siRNA for a combination of gene therapy and chemotherapy. Gold nanoparticles and nuclear imaging element are also used in the dendrimer building blocks of the nanocarrier platform so as to realize the in vivo real time CT and SPECT imaging in addition to cancer therapy. This study not only has the promise in terms of improving cancer diagnostic accuracy and therapeutic efficacy at the same time, but also shed light on the design and construction of multifunctional nanocarrier platform for wider biomedical applications.