Photochemically enhanced cellular delivery of cell penetrating peptide-PNA conjugates

Takehiko Shiraishi; Peter E. Nielsen

doi:10.1016/j.febslet.2006.01.077

Photochemically enhanced cellular delivery of cell penetrating peptide-PNA conjugates

Transcription, RNA, and Gene Medicine Program

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	FEBS Letters
Vol/bind	580
Udgave nummer	5
Sider (fra-til)	1451-6
Antal sider	6
ISSN	0014-5793
DOI	https://doi.org/10.1016/j.febslet.2006.01.077
Status	Udgivet - 20 feb. 2006

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10.1016/j.febslet.2006.01.077

Citationsformater

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title = "Photochemically enhanced cellular delivery of cell penetrating peptide-PNA conjugates",

abstract = "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.",

keywords = "Amino Acid Sequence, Cell Membrane Permeability, Cross-Linking Reagents, Drug Delivery Systems, Endosomes/metabolism, Gene Products, tat, HeLa Cells, Humans, Peptide Nucleic Acids/pharmacokinetics, Peptides/pharmacokinetics, Photochemistry/methods, Photosensitizing Agents/therapeutic use",

author = "Takehiko Shiraishi and Nielsen, {Peter E.}",

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doi = "10.1016/j.febslet.2006.01.077",

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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 - F E B S Letters

JF - F E B S Letters

IS - 5

ER -

Photochemically enhanced cellular delivery of cell penetrating peptide-PNA conjugates

Abstract

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