Intracellular Liquid-Liquid Phase Separation Induces Tunable Anisotropic Nanocrystal Growth for Multidimensional Analysis

Spatially directed biomineralization of nanocrystals for specific optical purposes in biological systems and elucidation of the mechanism of biomineralized nanocrystals remains a fascinating but extremely challenging task. Herein, the biomineralization of tunable gold nanocrystals with in situ protein coronas by intracellular liquid-liquid phase separation (LLPS) for in situ molecule surface-enhanced Raman spectrum (SERS) analysis and tumor fluorescence identification. The anisotropic nanocrystals are realized by regulating LLPS, in which the nucleation of nanocrystals is at the protein secondary structural site (beta-Corner) of the droplet, the different adsorption energies of crystal surfaces further promote the directional growth of nanocrystals. Interestingly, gold nanocrystals with ultra-narrow fluorescence emission at half-peak width and ultra-long Stokes shift and can obtain in situ molecular fingerprint information of protein corona to achieve by SERS. Of note are the anisotropic nanocrystals to differentiate clinical patient tumor tissue samples. Therefore, this study reveals the mechanism of intracellular tunable nanocrystal biomineralization and provides the basis for its biomedical application.