基于近红外二区成像的诊疗一体化有机纳米试剂及其在肿瘤联合治疗中的应用研究

In vivo fluorescence imaging in the second near-infrared window (NIR-II) is appealing due to minimal autofluorescence and negligible tissue scattering in this region, affording maximal penetration depth for deep tissue imaging with high feature fidelity. Conjugated polymer nanoparticles have emerged as a new class of photoacoustic or photothermal therapy agents due to their high absorption coefficients, good biocompatibilities, and good photostabilities. In this project, we will focus on the design of multifunctional theranostic agents based on organic conjugated polymer/oligomer nanoparticles and the application of NIR-II fluorescence imaging for tumor diagnosis. Firstly, we will design and synthesize new type conjugated polymer-based NIR-II materials. Second, we will adjust the molecular structure of conjugated oligomers to improve their optical properties. Finally, mutifunctional theranostic nanoparticles based on organic conjugated molecules will be prepared. By virtue of their synergistically combining theraputic ability and real-time diagnostic capability, this theranostic platforms will identify the location of tumor, detect the accumulation of theranostic agents, and monitor the therapeutic response as well as destroy tumors with higher specificity and sensitivity.

近红外二区（NIR-II）成像技术由于在体内荧光成像中可以穿透前所未有的深部组织及拥有很高的空间分辨率，在生物活体成像领域展现出巨大潜力。本项目瞄准NIR-II活体荧光成像和新型“诊疗一体化”多功能纳米试剂的开发与应用这两个前沿研究热点，利用有机共轭高分子这类新型光热及光声成像材料具有高消光系数、高光稳定性和良好生物相容性的特点，首先以设计开发新型的近红外二区有机共轭高分子，拓宽近红外二区有机材料的种类为前提，同时对有机共轭高分子和小分子结构进行优化，以获得高性能近红外二区有机共轭分子为目标。进一步根据肿瘤诊疗需求，按需构筑系列新型多功能诊疗一体化有机近红外二区纳米试剂，并利用协同效应，将多功能诊疗一体化有机纳米试剂用于二区成像指导的肿瘤联合治疗。利用近红外二区成像具有高分辨率、低自体荧光效应和高组织穿透深度的特点，在肿瘤协同治疗的同时，实现对肿瘤部位的诊断和检测，有效提高肿瘤诊疗效果。

构建高性能且生物相容性好的诊疗一体化试剂在纳米医学领域仍面临着很多挑战。有机共轭高分子纳米粒子由于具有优异光学性能、良好生物相容性和分子结构可调等特点使其成为一类非常有前景的新型光学诊疗试剂。本项目立足于高性能近红外二区成像纳米诊疗试剂的开发，围绕材料设计合成，纳米诊疗剂制备方法开发，按需构筑肿瘤多模式治疗及成像体系三个主要方向开展工作。首先通过给体-受体设计策略开发新型近红外二区有机共轭高分子材料，进一步调控近红外二区发射波长。针对有机共轭高分子纳米试剂的制备和表面功能化目前还局限于共沉淀法，其尺寸不可控、双亲性分子易解离和无法纯化等问题，我们设计开发了高稳定和尺寸均一可控SPNs诊疗剂制备方法，对基于SPNs的多功能纳米诊疗剂的可控制备提供了有效策略，有望对有机半导体纳米诊疗剂在生物医学领域的应用起到推动作用。在此基础上，进一步将纳米诊疗剂用于肿瘤治疗及成像，构建了系列多功能纳米诊疗平台，对影像指导肿瘤精准治疗具有重要意义。