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ACS Nano 2025, 19(25), 22953-22967

Nanorobot-Cell Communication via In Situ Generation of Biochemical Signals: Toward Regenerative Therapies

Achieving precise control of cellular processes drives possibilities for next-generation therapeutic approaches. However, existing technologies for influencing cell behavior primarily rely on specific drug delivery, limiting their ability to mimic natural cellular communication processes. In this work, we developed glucose-powered gold-silica (Au-SiO2) nanorobots that induce cell migration by generating steady-state hydrogen peroxide (H2O2) as a biochemical signaling molecule to mimic natural cellular communication with high spatial resolution. These nanorobots leverage the unique 2-in-1 catalytic activity of gold nanoparticles for glucose oxidation and H2O2 decomposition, allowing for precise control over the generation of steady-state H2O2 concentration and enhanced diffusion powered by glucose within the cellular microenvironment. We further demonstrated that at low dosages of nanorobots, the steady-state H2O2 generation promotes cell migration and proliferation, while higher dosages of nanorobots slow down cell proliferation. The proposed design of this biocompatible nanorobot is intended to enable communication with the environment and provide a noninvasive, biochemical command system for regulating cellular behavior. Additionally, we show proof of principle of a method by which nanorobots can augment wound healing and similar regenerative therapies.

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