2D Nano‐Photosensitizer Facilitates Proximity Labeling for Living Cells Surfaceome Deciphering

Photocatalytic proximity labeling has shown great promise for mapping the spatiotemporal dynamics of surfaceome. Although cell-surface targeting photosensitizers relying on antibodies, lipid molecules, and metabolic labeling have gained effects, the development of simpler and stable methods that avoid complex chemical synthesis and biosynthesis steps is still a huge challenge. Here, the study has introduced 2D nanomaterials with the ability of cell surface engineering to perform the in situ anchoring of photosensitizer on living cell surface. Photosensitizer can be stabilized on nanomaterials by coordination after one-step mixing, resulting in the nano-photosensitizer combining cell surface targeting ability and photosensitivity that allowing surface-specific proximity labeling. Nano-photosensitizer can be dispersed stably in aqueous solution, avoiding the defects of poor water solubility and aggregation of traditional organic photosensitizers. Singlet oxygen is generated locally under light irradiation, enabling spatiotemporally-resolved activating and labeling of cell surface proteome. Further application in the brain metastatic lung cancer has been found effective with numerous quantified differential cell surfaces proteins highly correlated with cancer metastasis and three potential players have been validated via immunoblotting and immunofluorescence, providing important insights for metastasis supported molecular mechanism.