Near‐Infrared Cocrystal Nanofluorophore with Enhanced Two‐Photon Absorption Cross Sections

ABSTRACT The growing demand for organic nanoprobes that combine broadband two‐photon absorption (TPA) with near‐infrared (NIR) optical excitation continues to drive advancements in biological imaging and advanced photonics. However, the design and preparation of such nanoprobe materials remain a significant challenge. Here, we employ co‐crystallization strategy to fabricate a TPA crystal material, BP4TC (donor BP4VA, acceptor TCNB), exhibiting deep red fluorescence. Nanoprecipitation with an amphiphilic surfactant yields water‐dispersible BP4TC nanoparticles (BP4TC‐NPs, ≈50 nm), which are subsequently used for open‐aperture Z‐scan measurements. This marks the first experimental determination of the TPA cross‐section for a molecular multicomponent solid. Prominent reverse‐saturable and saturable absorption characteristics span 700–1000 nm, with corresponding TPA cross‐sections decreasing monotonically with increasing wavelength. First‐principles calculations demonstrate that BP4TC exhibits a stronger intermolecular charge transfer capacity, verifying its enhanced TPA ability. The TPA cross‐section of BP4TC was further computed using the TDDFT approach, and the result indicates that BP4TC is a potent two‐photon absorber. Under 900 nm excitation, BP4TC‐NPs produce bright, low‐background fluorescence in A549 cells (human lung cancer cells), exhibiting negligible cytotoxicity. Notably, by combining broadband NIR‐I TPA with favorable biological properties, these cocrystal materials establish a multifunctional platform for biological multiphoton imaging and NIR photonics, while providing an experimentally validated blueprint for advanced nonlinear optical nanomaterials.