4.8 Article

Electrochemical Single-Cell Protein Therapeutics Using a Double-Barrel Nanopipette

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WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202215801

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Electrochemistry; Ionic Current Rectification; Protein Therapeutics; Single Cells; theta-Nanopipettes

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Single-cell protein therapeutics has the potential to enhance our understanding of how a specific protein treats cells individually instead of averaging across populations. A double-barrel nanopipette was used in this study to address the challenge. The results showed that delivering protein DJ-1 into cells can upregulate antioxidant protein and protect neural cells from oxidative stress. This nanotool provides a perspective for future single-cell therapies involving different therapeutic modalities.
Single-cell protein therapeutics is expected to promote our in-depth understanding of how a specific protein with a therapeutic dosage treats the cell without population averaging. However, it has not yet been tackled by current single-cell nanotools. We address this challenge by the use of a double-barrel nanopipette, in which one lumen was used for electroosmotic cytosolic protein delivery and the other was customized for ionic evaluation of the consequence. Upon injection of protein DJ-1 through the delivery lumen, upregulation of the antioxidant protein could protect neural PC-12 cells against oxidative stress from phorbol myristate acetate exposure, as deduced by targeting of the cytosolic hydrogen peroxide by the detecting lumen. The nanotool developed in this study for single-cell protein therapeutics provides a perspective for future single-cell therapeutics involving different therapeutic modalities, such as peptides, enzymes and nucleic acids.

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