Biomimetic graphitic carbon nitride nanoparticles for multiscale photomodulation and therapeutic intervention

Most organic matter on Earth originates from the conversion of solar energy through photosynthesis in chloroplasts. Here, drawing inspiration from photosynthesis, we develop hollow-sphere graphitic carbon nitride nanoparticles (hg-C3N4 NPs) that can modulate biological activity from subcellular processes to whole‑tissue function. The homogeneous hg-C3N4 NPs show responsiveness to light via both photoelectrochemical and photothermal mechanisms and can be spontaneously internalized with excellent cytocompatibility. Using a focusing laser, the hg-C3N4 NPs enable intracellular optical stimulation with subcellular resolution, inducing calcium-transient release in multiple cells and propagation in primary cardiomyocytes and cardiac fibroblasts. At the multicellular scale, optical pacing and synchronization of cardiomyocyte beating is readily achieved by light-emitting diodes. Further, we demonstrate that hg-C3N4 nanoparticles can be safely delivered and elicit measurable cortical and behavioural light responses in a model of advanced retinal degeneration. The application of hg-C3N4 NPs to porcine retinal tissue ex vivo confirms their modulation capability to directly activate retinal ganglion cell activity under light-emitting diode photostimulation. Taken together, hg-C3N4 NPs represent a versatile tool to address complex biomedical challenges through subcellular, intercellular and tissue-level photo-modulation. Biomimetic, non-genetic, light-responsive hollow-sphere graphitic carbon nitride nanoparticles can modulate biological activity from subcellular and cellular levels to whole-tissue function and enable therapeutic biomodulation in the retinas of visually impaired mice.