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

• Published in: Angewandte Chemie International Edition 2023-02, Vol.62 (9), p.e202215801-n/a
• Main Authors: Shi, Xiao‐Mei, Xu, Yi‐Tong, Zhou, Bing‐Yu, Wang, Bing, Yu, Si‐Yuan, Zhao, Wei‐Wei, Jiang, Dechen, Chen, Hong‐Yuan, Xu, Jing‐Juan
• Format: Article
• Language: English
• Subjects: 12-O-Tetradecanoylphorbol-13-acetate; Acetic acid; Cell- and Tissue-Based Therapy - methods; Electrochemistry; Hydrogen peroxide; Ionic Current Rectification; Ions; Nanoparticle Drug Delivery System; Nucleic acids; Oxidative Stress; Peptides; Protein Deglycase DJ-1 - pharmacology; Protein Deglycase DJ-1 - therapeutic use; Protein Therapeutics; Proteins; Single Cells; Tetradecanoylphorbol Acetate; θ-Nanopipettes
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202215801

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. Electrochemical single‐cell protein therapeutics was devised with an engineered θ‐nanopipette and exemplified by protein DJ‐1 enabled neuroprotection. Upon DJ‐1 injection 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 H2O2 by the detecting lumen.