Cell-Penetrating Peptides, Electroporation, and Drug Delivery

TL;DR

This paper reviews how cell-penetrating peptides like TAT facilitate drug delivery by possibly inducing molecular electroporation, offering targeted therapy options and expanding the potential for therapeutic cargo transport.

Contribution

It introduces the concept that transduction by CPPs may occur through molecular electroporation, providing new insights into their mechanism of cell entry and targeting strategies.

Findings

CPPs can carry therapeutic cargos over 500 Da

Electrostatic analysis suggests electroporation as a transduction mechanism

Targeting diseased cells enhances therapeutic specificity

Abstract

Certain short polycations, such as TAT and oligoarginine, rapidly pass through the plasma membranes of mammalian cells by a mechanism called transduction, as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) can carry with them cargos of 30 amino acids, more than the nominal limit of 500 Da and enough to be therapeutic. An analysis of the electrostatics of a charge outside the cell membrane and some recent experiments suggest that transduction may proceed by molecular electroporation. Ways to target diseased cells, rather than all cells, are discussed.