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

Angew Chem Int Ed Engl. 2023 Feb 20;62(9):e202215801. doi: 10.1002/anie.202215801. Epub 2023 Jan 24.

Abstract

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.

Keywords: Electrochemistry; Ionic Current Rectification; Protein Therapeutics; Single Cells; θ-Nanopipettes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell- and Tissue-Based Therapy* / methods
  • Ions
  • Nanoparticle Drug Delivery System
  • Oxidative Stress
  • Peptides
  • Protein Deglycase DJ-1* / pharmacology
  • Protein Deglycase DJ-1* / therapeutic use
  • Tetradecanoylphorbol Acetate

Substances

  • Ions
  • Peptides
  • Nanoparticle Drug Delivery System
  • Protein Deglycase DJ-1
  • Tetradecanoylphorbol Acetate