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Photochemically enhanced cellular delivery of cell penetrating peptide‐PNA conjugates
Author(s) -
Shiraishi Takehiko,
Nielsen Peter E.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.077
Subject(s) - cell penetrating peptide , internalization , hela , chemistry , peptide , in vivo , conjugate , cytosol , drug delivery , biophysics , nucleic acid , photosensitizer , in vitro , endosome , peptide nucleic acid , cell , biochemistry , microbiology and biotechnology , biology , enzyme , mathematical analysis , mathematics , organic chemistry
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, Arg 7 , KLA) in HeLa cells by a PCI approach using the photosensitizer AlPc 2a . 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.