Y1配体多模态分子探针在脑胶质瘤原位自组装增强诊治中的研究

脑胶质瘤是最严重的恶性脑肿瘤，具有发病率高、死亡率高和治愈率低的特点。基于脑胶质瘤特异性物的多模态分子探针为脑胶质瘤精准诊治提供了新的契机。本项目拟构建一种基于新型Y1配体和近红外七甲川花菁系列荧光分子NIRDye(800-1000nm)的多模态分子探针。该类探针能够通过新型Y1配体跨越血脑屏障特异性靶向脑胶质瘤，并在肿瘤微环境中过表达的MMP-2酶切作用下实现亲疏水结构的转变，通过肿瘤原位自组装增强探针在肿瘤区域的累积，提高近红外荧光/光声成像的灵敏度以及光热治疗效果，最终实现对脑胶质瘤的精准识别、边界确定及可视化的治疗。通过本项目的研究，有望为包括脑胶质瘤在内的Y1受体高表达脑肿瘤的临床精准诊治提供新的途径。

Glioma is the most severe brain tumor, with high morbidity and mortality worldwide. Biomarker-based multimodal molecular probe provides a novel strategy for glioma precision diagnosis and therapy. This project aims to develop a multimodal molecular probe based on novel Y1 receptor ligands and near-infrared fluorescent molecules NIRDye (800-1000nm). This molecular probe can cross blood brain barrier and specifically target glioma cells through Y1 receptor ligands, and response to the MMP-2 in the tumor microenvironment to alter the hydrophilic/lipophilic balance. The increased retention of molecular probe through in-situ self-assembling will improve the sensitivity of near-infrared fluorescence/photoacoustic imaging and the efficacy of photothermal therapy, achieving the accurate identification of glioma and its boundary, as well as the imaging-guided therapy. This study may pave a novel way for the precision diagnosis and therapy of Y1 receptor-overexpressed brain tumors.