Inkjet-Based Intracellular Delivery System that Effectively Utilizes Cell-Penetrating Peptides for Cytosolic Introduction of Biomacromolecules through the Cell Membrane

ACS Appl Mater Interfaces. 2023 Oct 18;15(41):47855-47865. doi: 10.1021/acsami.3c01650. Epub 2023 Oct 4.

Abstract

In the drug delivery system, the cytosolic delivery of biofunctional molecules such as enzymes and genes must achieve sophisticated activities in cells, and microinjection and electroporation systems are typically used as experimental techniques. These methods are highly reliable, and they have high intracellular transduction efficacy. However, a high degree of proficiency is necessary, and induced cytotoxicity is considered as a technical problem. In this research, a new intracellular introduction technology was developed through the cell membrane using an inkjet device and cell-penetrating peptides (CPPs). Using the inkjet system, the droplet volume, droplet velocity, and dropping position can be accurately controlled, and minute samples (up to 30 pL/shot) can be carried out by direct administration. In addition, CPPs, which have excellent cell membrane penetration functions, can deliver high-molecular-weight drugs and nanoparticles that are difficult to penetrate through the cell membrane. By using the inkjet system, the CPPs with biofunctional cargo, including peptides, proteins such as antibodies, and exosomes, could be accurately delivered to cells, and efficient cytosolic transduction was confirmed.

Keywords: Inkjet system; cell-penetrating peptides; cytosolic delivery; macromolecules; membrane penetration.

MeSH terms

  • Cell Membrane / metabolism
  • Cell-Penetrating Peptides* / chemistry
  • Cytosol / metabolism
  • Drug Delivery Systems
  • Endocytosis

Substances

  • Cell-Penetrating Peptides