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.
authors.affiliation: Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Blegdamsvej 3c, 2200 Copenhagen N, Denmark.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nielsen
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D011992:Endosomes / Q000378:metabolism; D015696:Gene Products, tat; D006367:HeLa Cells; D006801:Humans; D020135:Peptide Nucleic Acids / Q000493:pharmacokinetics*; D010455:Peptides / Q000493:pharmacokinetics*; D010777:Photochemistry / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use
chemical_list: D003432:Cross-Linking Reagents; D015696:Gene Products, tat; D020135:Peptide Nucleic Acids; D010455:Peptides; D017319:Photosensitizing Agents; C015462:polyarginine