We report the first demonstration of ground-state proton transfer (GSPT) as a strategy to enhance and red-shift the two-photon absorption (TPA) cross-section of a phototrigger into the near-infrared (NIR) region without chemical modification. By leveraging GSPT in a simple binol-based system, we developed an aggregation-induced emission (AIE)-fluorogenic phototrigger with a large two-photon uncaging (TPU) cross-section within the phototherapeutic window. This design enables efficient NIR light-triggered release of bioactive molecules with high spatiotemporal precision. As proof of concept, we successfully applied our phototrigger for the uncaging of two distinct anticancer drugs—valproic acid and chlorambucil—under two-photon excitation. The system exhibits strong GSPT due to the presence of two hydroxyl groups, leading to significant enhancement in TPU efficiency. Upon irradiation with either visible or NIR light, up to two equivalents of drug are released per trigger molecule, significantly increasing intracellular payload delivery. Moreover, the phototrigger displays AIE behavior arising from restricted rotation of the naphthol moieties, which suppresses nonradiative decay and enhances fluorescence upon aggregation. Notably, a distinct fluorogenic color change—from yellow to green—is observed following drug release, enabling real-time monitoring of the uncaging process.144701-48-4 medchemexpress The photophysical properties were systematically investigated through UV-vis and fluorescence spectroscopy across various solvents and pH conditions.CD34 Antibody Description A clear red shift in absorbance and emission maxima was attributed to the formation of bisnaphthoxide ions via GSPT in aqueous environments. TPA measurements using the open-aperture z-scan technique confirmed substantial TPA cross-sections of up to 110 GM for Binol-VPA and 140 GM for Binol-Cbl at 800 nm, with values exceeding 20 GM at 810 nm—well above the threshold required for cellular applications.PMID:34823313 Photochemical quantum yields reached 0.34 and 0.39, respectively, indicating efficient photoactivation. Controlled experiments under “light on-off” conditions confirmed that drug release is exclusively light-dependent. In vitro studies using B16F10 melanoma cells demonstrated enhanced cytotoxicity only upon illumination, with IC50 values dropping significantly after light exposure. Confocal microscopy revealed lysosomal localization of the phototrigger, consistent with endocytic uptake. Real-time fluorescence imaging in MCF-7 cells captured the dynamic transition from yellow to green fluorescence upon irradiation, confirming successful drug release. These findings establish GSPT as a powerful, modifiable, and synthetically accessible approach to engineer high-performance two-photon phototriggers for advanced biomedical applications such as targeted drug delivery and live-cell imaging.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com