Spatially resolved in situ tagging of the cell of interest is crucial for in-depth mechanistic dissection of multicellular architectures or processes. With continuing interest in bioorthogonal photocatalytic decaging chemistry, we herein report the extracellular-targeted photocatalytic decaging system (CAT-Ex) for spatially resolved cell tagging and surface proteome profiling under living conditions. An antibody-conjugated photocatalysis system was established and extensively validated, enabling photocatalytic decaging of biotin precursors and proximal quinone methide probes on target cells. Visible-light-controlled selective cell tagging in cell mixture as well as in primary cells from tumor xenografts were demonstrated. Spatially resolved membrane proteome profiling was further achieved by coupling quinone methide decaging chemistry with CAT-Ex, revealing a potential microdomain protein cluster surrounding the endogenous HER2 receptor. Finally, we expanded our strategy to photocatalytic prodrug decaging for selective tumor cell killing, establishing CAT-Ex as a general platform for diverse photo-controlled molecular manipulations on targeted cells with spatial-temporal precision.

原位空间解析感兴趣的细胞的标记对于多细胞结构或过程的深入机械解剖至关重要。随着对生物正交光催化降解化学的持续关注，我们在此报告了用于在生活条件下进行空间分辨细胞标记和表面蛋白质组分析的细胞外靶向光催化降解系统 (CAT-Ex)。建立并广泛验证了抗体偶联光催化系统，使生物素前体和近端醌甲基化物探针在靶细胞上的光催化降解成为可能。证明了在细胞混合物以及来自肿瘤异种移植物的原代细胞中的可见光控制的选择性细胞标记。通过将甲基醌去壳化学与 CAT-Ex 结合，进一步实现了空间分辨的膜蛋白质组分析，揭示了围绕内源性 HER2 受体的潜在微域蛋白簇。最后，我们将我们的策略扩展到用于选择性杀伤肿瘤细胞的光催化前药降解，将 CAT-Ex 建立为具有时空精度的靶细胞上各种光控分子操作的通用平台。