Photopharmacology is a booming research area requiring a new generation of agents possessing simultaneous functions of photoswitching and pharmacophore. It is important that any practical implementation of photopharmacology ideally requires spatial control of the medicinal treatment zone. Thus, advances in the study of substances meeting all the listed requirements will lead to breakthrough research in the coming years. In this study, CQDs@phosphonate nanohybrids are presented for the first time and combine biocompatible and nontoxic luminescent carbon quantum dots (CQDs) with photoactive phosphonate enabling inhibition of butyrylcholinesterase (BChE), which is a prognostic marker of numerous diseases. The conjunction of these components in hybrids maintains photoswitching and provides enhancement of BChE inhibition. After laser irradiation with a wavelength of 266 nm, CQDs@phosphonate hybrids demonstrate a drastic increase of butyrylcholinesterase inhibition from 38% up to almost 100% and a simultaneous luminescence decrease. All the listed hybrid properties are demonstrated not only for in vitro experiments but also for complex biological samples, i.e., chicken breast. Thus, the most important achievement is the demonstration of hybrids characterized by a remarkable combination of all-in-one properties important for photopharmacology: (i) bioactivity toward butyrylcholinesterase inhibition, (ii) strong change of inhibition degree as a result of laser irradiation, luminescence as an indicator of (iii) bioactivity state, and of (iv) spatial localization on the surface of a sample.

Light-responsive materials enabling external modulation of bioactivity and spatial control are highly requested for photopharmacology—a booming research area of modern medicine. We present organo-inorganic hybrids of photoswitchable, bioactive symmetric diamine-phosphine oxides conjugated with luminescent carbon quantum dots (CQDs). The phosphonate compound was found to undergo Z-E isomerization upon 266 nm laser irradiation and exhibit butyrylcholinesterase (BChE) inhibition that increases twofold (15–30%) after photoconversion. Hybrids were fabricated via physical adsorption and chemisorption using different CQD surface groups, and characterized by UV-Vis, luminescence, and FTIR spectroscopy, confirming hybrid formation and retention of functional properties. In both binding modes, the molecules retained photoswitching capability despite steric constraints. All hybrids displayed orthogonal functions: luminescence (excitation at 350 nm) and photomodulation of BChE inhibition (at 266 nm). Remarkably, the binding mode dictated the bioactivity window—chemisorbed hybrids showed narrow 1.5-fold modulation, whereas physisorbed hybrids exhibited ultra-wide >10-fold modulation. This tunable responsiveness, achieved simply by altering the binding mode, demonstrates the exceptional potential of this hybrid design strategy for developing photoswitchable materials with tailored photopharmacological performance.