巨噬细胞通过极化成不同的表型，执行多种功能，如病原体吞噬、抗原呈递以及组织重塑。动态观察巨噬细胞表型对于评估疾病进展和药物候选物治疗反应至关重要。然而，目前的技术无法在体内鉴定巨噬细胞表型。在这项研究中，我们开发了一种表面增强拉曼散射纳米探针，命名为AH1，通过比率拉曼信号实现对生理pH值的准确测定，具有高敏感性和组织穿透深度。由于表型依赖性的代谢重构，AH1可以通过测量吞噬体酸度水平有效鉴定巨噬细胞亚群。经静脉注射后，AH1不仅可以可视化小鼠模型的脑肿瘤和癫痫区域中巨噬细胞表型的空间分布，还可以揭示药物干预后脑损伤中巨噬细胞的重新极化过程。该研究为动态监测与疾病相关的免疫微环境以及评估体内免疫治疗的疗效提供了一种新工具。本文受版权保护，版权所有。

Macrophage performs multiple functions such as pathogen phagocytosis, antigen presentation and tissue remodeling by polarizing toward a spectrum of phenotypes. Dynamic imaging of macrophage phenotypes is critical for evaluating disease progression and the therapeutic response of drug candidates. However, current technologies cannot identify macrophage phenotypes in vivo. Here, we develop a surface-enhanced Raman scattering (SERS) nanoprobe, AH1, which enables the accurate determination of physiological pH with high sensitivity and tissue penetration depth through ratiometric Raman signals. Due to the phenotype-dependent metabolic reprogramming, AH1 can effectively identify macrophage subpopulations by measuring the acidity levels in phagosomes. After intravenous administration, AH1 not only visualizes the spatial distribution of macrophage phenotypes in brain tumors and epileptic regions of mouse models, but also reveals the repolarization of macrophages in brain lesions after drug intervention. This work provides a new tool for dynamically monitoring the disease-associated immune microenvironment and evaluating the efficacy of immune-therapeutics in vivo. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.