Biomimic opto-nanobiointerface enables multiscale biomodulation
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Virtually all organic material on Earth has been produced converting solar energy through photosynthesis in chloroplasts, a sack-like, double membrane organelle in plants and algae, where transmembrane electron transfer occurs from lumen to stroma. Although animals hardly harness the power of photosynthesis, their bioelectrical signals extensively regulate complex electrophysiological behaviors, rendering it a superior target for biomedical innovation. Here a crude structural mimicry of chloroplast has led us to discover that hollow sphere graphitic carbon nitride nanoparticles (hg-C 3 N 4 NPs) endowed non-genetic, subcellular and intercellular photo-modulation of various excitable and non-excitable cells, accumulatively achieving modulation at tissue/organ function level. The homogeneous hg-C 3 N 4 NPs showed photo-responsiveness via photoelectrochemical and photothermal mechanisms under photocurrent measurement. The hg-C 3 N 4 NPs can be spontaneously internalized with excellent cytocompatibility. Using a focusing laser, the hg-C 3 N 4 NPs enable intracellular optical stimulation with subcellular resolution, inducing calcium transient release in multiple cells and propagation in primary cardiomyocytes and cardiac fibroblasts. At multicellular scale, optical pacing and synchronization of cardiomyocyte beating is achieved facilely by LED. Further, we demonstrate that hg-C 3 N 4 NPs can be safely injected into mouse eyes, restoring light sensitivity in blind mice. Finally, application of hg-C 3 N 4 NPs to porcine retinal tissue ex vivo confirmed their modulation capability to reactivate RGCs activity under LED photostimulation. Taken together, these nanostructured biomimic semiconductor NPs offer high resolution, leadless optical probing, non-invasive delivery and great biocompatibility, serving as a versatile tool for addressing a range of complex biomedical challenges through subcellular, intercellular and tissue-level photo-modulation across a broad spectrum of scales.