长余辉纳米疫苗的构建及其在免疫细胞示踪和肿瘤治疗中的应用

Immunotherapy is the most promising way to solve the bottleneck problems in traditional cancer treatments. Highly sensitive tracking immune cells and immunotherapy-based combined therapy are the predominant challenges in developing multifunctional vaccines. Near-infrared persistent luminescence nanoparticles (NIR PLNPs) have unique advantages of no need for in situ excitation, high signal-to-noise ratio, persistent luminescent renewability and internal light induced photodynamic therapy. We plan to engineer novel PLNPs-based multifunctional nanovaccines for high sensitive tracking of dendritic cells in vivo and high-efficient photodynamic-immunotherapy of tumors. Monomodal and Multimodal imageable persistent luminescent nanovaccines, and photosensitizer/immunostimulant co-modified PLNPs nanovaccine will be fabricated for labelling and tracking of dendritic cells (optical and multimodal imaging), and combined photodynamic-immunotherapy of tumors. The project will broaden the applications of PLNPs in immune cell tracking and immunotherapy, enrich the strategy for designing multifunctional nanovaccines, and provide new methodologies to solve the key problems in the field of vaccine-based immunotherapy.

免疫治疗是目前最有希望解决传统癌症治疗方法瓶颈的新兴治疗方法，其中高灵敏的免疫细胞示踪和肿瘤协同治疗是目前多功能纳米疫苗研究领域的关键问题。近红外长余辉纳米材料具有免原位激发、高信噪比、余辉可活化以及可作为光动力学治疗的内在持续光源等独特性能。本项目旨在充分利用长余辉纳米材料的独特性能，构建多功能长余辉纳米疫苗并研究其在免疫示踪和肿瘤治疗方面的应用。拟以长余辉纳米材料作为低背景光学成像探针和引发光动力治疗的内在光源，构建单模态成像长余辉纳米疫苗、多模态成像长余辉纳米疫苗和长余辉发光活化光动力学/免疫联合治疗疫苗并用于高灵敏的免疫细胞示踪和高效安全的成像引导肿瘤联合治疗。本项目的实施将拓展性能独特的长余辉纳米材料在肿瘤免疫学方面的应用，丰富设计纳米疫苗的策略，提供新的方法学来解决纳米疫苗领域的问题。

本项目一方面以长余辉材料作为低背景光学成像探针和引发光动力治疗的内在光源，基于变固为胶策略构建了长余辉凝胶和长余辉免疫凝胶，应用于超强长余辉发光引导和激发的肿瘤光动力学治疗和光动力学/免疫联合治疗，解决了在长余辉材料在生物应用中发光性能和生物利用度难以兼容的难题。另一方面，基于生物活性分子引导合成策略发展高效低毒的诊疗探针。以生物体内固有或FDA批准临床应用的生物活性分子作为结构和功能导向单元，开发了若干制备简单高效、易于规模化生产、生物相容性良好、性能优良的诊疗探针。本项目的研究成果为高效的肿瘤诊疗提供了新方法和新策略。在本领域主流期刊上发表相关论文11篇（包括Advanced Functional Materials 1篇, Biomaterials 2篇, Chemical Engineering Journal 1篇），申请国家发明专利1项，完成了预定的研究目标。