Unlocking NIR‐II Photoluminescence in 2D Copper Tetrasilicate Nanosheets through Flame Spray Synthesis

Abstract Expanding fluorescence bioimaging into the second near‐infrared spectrum (NIR‐II, 1000–1700 nm) unlocks advanced possibilities for diagnostics and therapeutics, offering superior tissue penetration and resolution. 2D copper tetrasilicate (CTS) pigments ( M CuSi 4 O 10 , M = Ca, Sr, Ba) are known for their brightness and stability, yet synthetic challenges have curbed their integration into bioimaging. Here, flame‐spray‐pyrolysis (FSP) is introduced as a versatile and scalable synthesis approach to produce ultra‐bright, metastable CTS nanosheets (NS) by annealing multi‐element metal oxide nanoparticles into 2D crystals through calcination or laser irradiation. Group‐II ion incorporation shifts emission into the NIR‐II range, with Ba 0.33 Sr 0.33 Ca 0.33 CuSi 4 O 10 peaking at 1007 nm, while minor Mg‐doping induces a hypsochromic shift and extends fluorescence lifetimes. The engineered CTS achieves quantum yields of up to 34%, supporting NS high‐frame‐rate imaging (> 200 fps). These unique properties enable CTS‐NS to serve as powerful contrast agents for super‐resolution NIR bioimaging, demonstrated in vivo through transcranial microcirculation mapping and macrophage tracking in mice using diffuse optical localization imaging (DOLI). This pioneering synthesis strategy unlocks wavelength‐tunable NS for advanced NIR‐II bioimaging applications.