研发多模态成像及联合治疗方法一体化的实体肿瘤诊疗体系

目前恶性肿瘤已经严重威胁到人类生命与健康，但缺乏有效的治疗手段。肿瘤免疫疗法通过激活患者自身的免疫系统杀灭肿瘤细胞，比肿瘤传统治疗法（手术/放疗/化疗）有着明显优势，但实体瘤存在肿瘤免疫抑制微环境，大大降低了现有免疫治疗技术的有效性。肿瘤免疫治疗技术的研发也面临着瓶颈问题，比如缺乏可视化技术研究免疫细胞与肿瘤的相互作用和临床相关的人源化实体瘤模型。目前可视化的纳米诊疗平台也存在着困难，急需开发多模态引导的多治疗手段于一体的可视化肿瘤诊疗剂，且纳米材料易被人体清除难以实现其在体内长循环和肿瘤部位高效富集。针对这些肿瘤诊疗领域的挑战，基于前期研究基础，本项目将构建免疫系统人源化实体瘤模型，研发集光声成像、核磁成像、光热治疗、光动力治疗、基因治疗/化疗及免疫治疗于一体的可视化诊疗方案，有望打破肿瘤免疫抑制微环境，同时解决可视化纳米材料靶向肿瘤和被机体清除等瓶颈问题。

Malignant tumors remain a major threat to human health and life, and still lack effective therapy. Tumor immunotherapy possesses obvious advantages over the traditional tumor therapies (surgery / radiotherapy / chemotherapy) by activating the patient's own immune system to eliminate tumor cells. However, the existence of immunosuppressive microenvironment within solid tumors significantly reduces the efficacy of tumor immunotherapy. There are many bottlenecks in the development of cancer immunotherapy, such as the lack of visualization technology to reveal the interaction between the immune cells and cancer cells as well as the lack of immune system humanized solid tumor models. There are also bottlenecks in the development of visualizable nanotheranostic agents, such as the urgent need for visualizable multimodal nanotheranostic agents that can combine multiple therapeutics for malignant tumors. In addition, the rapid clearance of nanomaterials by the human body makes it difficult to achieve high levels of enrichment of nanomaterials within the tumors and extended presence in circulation. To resolve these bottlenecks in the development of tumor visualization technology and tumor immuotherapy based on our research expertise, this project will establish immune system humanized solid tumor mouse models, and use these models to develop a visualizable nanotheranostic agent that integrates photoacoustic imaging, magnetic resonance imaging, photothermal therapy, photodynamic therapy, gene therapy/chemotherapy, and immunotherapy for the treatment of solid tumors. This integrated therapeutic approach will help to disrupt the immune suppressive microencironment within solid tumors and resolve the bottlenecks of the low enrichment of visualizable nanomaterials in tumors and their short half-life in circulation.