Key Laboratory of Smart Drug Delivery Ministry of Education, Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education, School of Pharmacy, Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 201203, China.
School of Information Science and Technology, Fudan University, Shanghai, 200438, China.
Adv Sci (Weinh). 2023 Oct;10(28):e2304020. doi: 10.1002/advs.202304020. Epub 2023 Aug 6.
Accurate delineation of glioma infiltrative margins remains a challenge due to the low density of cancer cells in these regions. Here, a hierarchical imaging strategy to define glioma margins by locating the immunosuppressive tumor-associated macrophages (TAMs) is proposed. A pH ratiometric fluorescent probe CP2-M that targets immunosuppressive TAMs by binding to mannose receptor (CD206) is developed, and it subsequently senses the acidic phagosomal lumen, resulting in a remarkable fluorescence enhancement. With assistance of CP2-M, glioma xenografts in mouse models with a tumor-to-background ratio exceeding 3.0 for up to 6 h are successfully visualized. Furthermore, by intra-operatively mapping the pH distribution of exposed tissue after craniotomy, the glioma allograft in rat models is precisely excised. The overall survival of rat models significantly surpasses that achieved using clinically employed fluorescent probes. This work presents a novel strategy for locating glioma margins, thereby improving surgical outcomes for tumors with infiltrative characteristics.
由于这些区域癌细胞密度低，因此准确描绘神经胶质瘤浸润性边界仍然是一个挑战。在这里，提出了一种分层成像策略，通过定位免疫抑制性肿瘤相关巨噬细胞（TAMs）来定义神经胶质瘤边界。开发了一种 pH 比率荧光探针 CP2-M，它通过与甘露糖受体（CD206）结合来靶向免疫抑制性 TAMs，随后它可以感应酸性吞噬体腔，从而导致荧光显著增强。在 CP2-M 的辅助下，成功地在具有肿瘤与背景比超过 3.0 的小鼠模型中的神经胶质瘤异种移植物中进行了长达 6 小时的可视化。此外，通过在开颅手术后对暴露组织的 pH 分布进行术中映射，可以精确切除大鼠模型中的同种异体移植物。大鼠模型的总生存率明显超过了临床使用的荧光探针所达到的水平。这项工作提出了一种定位神经胶质瘤边界的新策略，从而改善了具有浸润特征的肿瘤的手术结果。
