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.
| Original language | English |
|---|---|
| Journal | FEBS Letters |
| Volume | 580 |
| Issue number | 5 |
| Pages (from-to) | 1451-6 |
| Number of pages | 6 |
| ISSN | 0014-5793 |
| DOIs | |
| Publication status | Published - 20 Feb 2006 |
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