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Gold-modified nanoporous silicon for photoelectrochemical regulation of intracellular condensates

Abstract

Nano-enabled catalysis at the interface of metals and semiconductors has found numerous applications, but its role in mediating cellular responses is still largely unexplored. Here we explore the territory by examining the once elusive mechanism through which a nanoporous silicon-based photocatalyst facilitates the two-electron oxidation of water to generate hydrogen peroxide under physiological conditions. We achieve precise modulation of intracellular stress granule formation by the controlled photoelectrochemical production of hydrogen peroxide in the extracellular environment, thereby enhancing cellular resilience to significant oxidative stress. This photoelectrochemical strategy has been evaluated for its efficacy in treating myocardial ischaemia–reperfusion injury in an ex vivo rodent model. Our data suggest that a pretreatment regimen involving photoelectrochemical generation of hydrogen peroxide at mild concentrations mitigates myocardial ischaemia–reperfusion-induced functional decline and infarction. These findings suggest a viable wireless therapeutic intervention for managing ischaemic disease and highlight the biomedical potential of nanostructured semiconductor-based catalytic devices.

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Fig. 1: Design concept for the H2O2 photocatalyst and proposed mechanism for photoelectrochemical H2O2 production as a therapeutic strategy against myocardial I/R injury.
Fig. 2: Theoretical predictions for Au/Si and Au/por-Si photocatalysis.
Fig. 3: Fabrication and characterization of Au/por-Si interfaces.
Fig. 4: Electrochemical and photocatalytic analysis of Au/Si and Au/por-Si interfaces.
Fig. 5: Au/Si and Au/por-Si photocatalysis enables modulation of SG assembly and enhanced oxidative stress adaptation.
Fig. 6: Au/Si and Au/por-Si photocatalysis protects heart tissue from I/R injury.

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Data availability

The research findings presented in this study are supported by data included in the main text and in Supplementary Information. Source data are publicly available at https://osf.io/fkum8/. Source data are provided with this paper.

Code availability

Scripts used for data analysis in this study can be accessed from https://osf.io/fkum8/.

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Acknowledgements

We thank K. M. Watters for scientific editing of the paper. This work was supported by the US Army Research Office (W911NF-21-1-0090), the US National Science Foundation (NSF CBET-2422962, NSF CBET-2128140 and NSF OMA-2121044) and the National Institutes of Health (1R56EB034289-01 and 1R01EB036091-01). B.T. acknowledges the support from Chan Zuckerberg Biohub Chicago Spoke Award. P.L. acknowledges the support from the Grier Prize for Biophysical Sciences Innovation. We acknowledge the support from the Materials Research Science and Engineering Center (NSF DMR-2011854). S.S. gratefully acknowledges the support from the Natural Sciences and Engineering Research Council (NSERC) of Canada (discovery grant number RGPIN-2023-05298). Acknowledgement is made to BioRender (www.biorender.com) for creating the schematics in Figs. 1, 3 and 6. This work made use of the Pritzker Nanofabrication Facility at the Pritzker School of Molecular Engineering at the University of Chicago, which receives support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), a node of the National Science Foundation’s National Nanotechnology Coordinated Infrastructure. We thank F. Shi (University of Illinois Chicago) and Y. Fang (Tongji University) for help on the STEM imaging; this work made use of instruments in the Electron Microscopy Service (Research Resources Center, University of Illinois Chicago).

Author information

Authors and Affiliations

Authors

Contributions

B.T. and S.S. supervised the research. J.Z. and B.T. initiated and conceived the idea. J.Z. conducted the majority of data collection on materials synthesis, characterization and animal experiments. P.L. and W.L. assisted with material preparation and characterization. A.K. and S.S. conducted the computational analysis and interpretation. J.Y., L.M. and Z.C. assisted with the in vitro and ex vivo experiments. P.L. assisted with the in vivo electrophysiology experiments. C.Y. and S.K. assisted with imaging. J.Z. and P.L. conducted all the subsequent data analysis. J.Z. and B.T. prepared the paper with input from all the other authors.

Corresponding authors

Correspondence to Jing Zhang, Samira Siahrostami or Bozhi Tian.

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Nature Nanotechnology thanks Ying Fang, Brian Timko and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Tables 1 and 2, Figs. 1–61 and legends for Supplementary Video 1, Supplementary Methods and Supplementary Discussion.

Reporting Summary

Supplementary Video 1

Interface formation between Au/por-SiNWs and U2OS cells capable of initiating SG assembly.

Supplementary Data 1

The file Jing Zhang_Supplementary Data 1.xls contains statistical source data of Jing Zhang_SI.

Supplementary Data 2

The file Jing Zhang_Supplementary Data 2.zip contains the raw ECG signal data shown in Supplementary Fig. 61.

Supplementary Code 1

ECG signal analysis code.

Source data

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Fig. 5

Statistical source data.

Source Data Fig. 6

Statistical source data, LVP and ECG signal raw data and unprocessed western blots.

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Zhang, J., Li, P., Yue, J. et al. Gold-modified nanoporous silicon for photoelectrochemical regulation of intracellular condensates. Nat. Nanotechnol. 20, 835–844 (2025). https://doi.org/10.1038/s41565-025-01878-4

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