双靶向多模态纳米诊疗剂用于影像引导的脑胶质瘤精准切除和残留灶光热治疗研究

Gliomas are the most common primary malignant brain tumors with invasive growth, and the 5-year survival rate is less than 10% after surgery combined with radio- and chemo-therapy. How to precisely detect tumor margins and effectively treat residual foci is challenging. Multimodal imaging-guided targeted therapy holds the potential for the glioma treatment. In this project, we intends to build a new class of multi-functional theranostic nanoprobes with high sensitivity, high specificity and high-resolution. With the aid of magnetic resonance imaging, photoacoustic imaging and Raman imaging, the probes can facilitate pre-operative early diagnosis of brain tumors, intra-operative accurate detection of tumor margins, and imaging-guided precise resection of tumor and photothermal therapy of residual foci, as well as post-operative real-time assessment on therapeutic efficacy. Our project will diversify the study of glioma cancer and provide new preclinical evidence for the early diagnosis and precision therapy of glioma.

脑胶质瘤是最常见的原发性颅内恶性肿瘤，呈浸润性生长，手术及放化疗后5年生存率不足10%。如何精确定位脑胶质瘤边界和精准治疗术后残留灶是国内外脑疾病领域的一个挑战性问题，而基于分子影像的诊疗一体化为脑胶质瘤的边界精确识别和精准治疗带来新的希望。本项目拟构建一类新型高灵敏度、高特异性、高分辨率的多功能纳米诊疗剂，结合磁共振成像、光声成像和拉曼成像手段，实现对脑肿瘤的术前早期诊断、术中边界精确识别、分子影像引导的肿瘤术中精准切除和残留灶的光热靶向治疗、以及术后实时影像评估，建立以多模态分子影像为基础的脑胶质瘤精准诊疗和疗效评估体系，为临床上脑胶质瘤的早期诊断和精准治疗提供理论指导和参考依据。

如何精确定位脑胶质瘤边界和精准治疗术后残留灶是国内外脑疾病领域的一个挑战性问题，而基于分子影像的诊疗一体化为脑胶质瘤的边界精确识别和精准治疗带来新的希望。本项目首先通过“三叉戟”策略构筑CT/MRI/光声三模融合分子影像探针，实现对脑胶质瘤术前诊断信息的精确获取；然后通过酸性“代谢边界”导航策略构筑代谢微酸响应型高灵敏拉曼探针，实现脑胶质瘤术中边界的精准识别和肿瘤切除；最后通过 “按需响应”的智能化策略构筑代谢微酸响应的纳米诊疗消融探针，实现脑胶质瘤术后残留灶的靶向光热消融彻底治疗。在此基础上，针对制约脑胶质瘤诊疗效率的痛点问题进行拓展研究：针对如何高效突破血脑屏障的问题，开发出“二元协同”的狂犬病毒仿生递送策略，仿生探针比目前探针的脑靶向效率提高了3倍多；针对如何缓解化疗抵抗的问题，开发出仿生中性粒细胞的高效协同化学动力学疗法增敏化疗策略。旨在建立以多模态融合与智能化响应为基础的脑胶质瘤精准高效诊疗平台，为临床上脑胶质瘤的精准切除和高效治疗提供理论指导和参考依据。