Transdermal delivery of proteins mediated by non-covalently associated arginine-rich intracellular delivery peptides.
Plasma membranes of animal cells are generally impermeable to macromolecules. Protein transduction mediated by protein transduction domains (PTDs) covalently cross-linked to cargoes for cellular internalization has previously been demonstrated. Peptides with PTDs could be an effective way to deliver proteins into living cells or tissues in vitro. In this report, we demonstrate that arginine-rich intracellular delivery (AID) peptides are able to facilitate the delivery of proteins into animal cells and to penetrate skin tissues rapidly. This cellular internalization and transdermal delivery of proteins is mediated by non-toxic AID peptides in a non-fusion protein and non-conjugation dependent manner. The efficiency of intracellular transport is further increased in the presence of chemical enhancer oleic acid. The mechanism of the AID-mediated cellular entry may involve macropinocytosis and actin rearrangement. Thus, we confirm that direct delivery of bioactive proteins into living cells and tissues mediated by non-covalent actions of AID peptides represents a useful strategy in pharmaceutics, therapeutics and cosmetics.
Hou
Yu-Wun
YW
Department of Life Science, National Dong Hwa University, Hualien, Taiwan.
Chan
Ming-Huan
MH
Hsu
Hui-Ru
HR
Liu
Betty Revon
BR
Chen
Chung-Pin
CP
Chen
Hwei-Hsien
HH
Lee
Han-Jung
HJ
D000279:Administration, Cutaneous; D000818:Animals; D001120:Arginine; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D004337:Drug Carriers; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010455:Peptides; D010957:Plasmids; D021381:Protein Transport
D004337:Drug Carriers; D010455:Peptides; D049452:Green Fluorescent Proteins; D001120:Arginine