Photochemically enhanced cellular delivery of cell penetrating peptide-PNA conjugates

TY - JOUR

T1 - Photochemically enhanced cellular delivery of cell penetrating peptide-PNA conjugates

AU - Shiraishi, Takehiko

AU - Nielsen, Peter E.

PY - 2006/2/20

Y1 - 2006/2/20

N2 - Recent studies have shown that endosomal release is a major rate-limiting step for cellular delivery via a variety of cationic cell penetrating peptides. Thus, methods and/or protocols for effective release of endosomally entrapped drugs are highly warranted. Photochemical internalization (PCI) has previously been proposed for this purpose. Here, we demonstrate an enhancement of up to two orders of magnitude of the antisense effects (cytosolic/nuclear) of peptide nucleic acid-peptide conjugates (Tat, Arg7, KLA) in HeLa cells by a PCI approach using the photosensitizer AlPc2a. These results emphasize the importance of endosomal release for cellular activity of this type of drug delivery and also raise hope that methods like PCI which have applications for in vivo use may also enhance the bioavailability and in vivo efficacy of these types of conjugates.

AB - Recent studies have shown that endosomal release is a major rate-limiting step for cellular delivery via a variety of cationic cell penetrating peptides. Thus, methods and/or protocols for effective release of endosomally entrapped drugs are highly warranted. Photochemical internalization (PCI) has previously been proposed for this purpose. Here, we demonstrate an enhancement of up to two orders of magnitude of the antisense effects (cytosolic/nuclear) of peptide nucleic acid-peptide conjugates (Tat, Arg7, KLA) in HeLa cells by a PCI approach using the photosensitizer AlPc2a. These results emphasize the importance of endosomal release for cellular activity of this type of drug delivery and also raise hope that methods like PCI which have applications for in vivo use may also enhance the bioavailability and in vivo efficacy of these types of conjugates.

KW - Amino Acid Sequence

KW - Cell Membrane Permeability

KW - Cross-Linking Reagents

KW - Drug Delivery Systems

KW - Endosomes/metabolism

KW - Gene Products, tat

KW - HeLa Cells

KW - Humans

KW - Peptide Nucleic Acids/pharmacokinetics

KW - Peptides/pharmacokinetics

KW - Photochemistry/methods

KW - Photosensitizing Agents/therapeutic use

U2 - 10.1016/j.febslet.2006.01.077

DO - 10.1016/j.febslet.2006.01.077

M3 - Journal article

C2 - 16460737

SN - 0014-5793

VL - 580

SP - 1451

EP - 1456

JO - FEBS Letters

JF - FEBS Letters

IS - 5

ER -