TAT-liposomes: a novel intracellular drug carrier.
TAT peptide was attached to the surface of plain and PEGylated liposomes. These TAT peptide-modified liposomes have been shown to translocate into a variety of normal and cancer cells if a non-hindered interaction between the cell surface and liposome-attached TAT peptide was made possible. TAT peptide-liposomes translocated into cells remain intact within first few hours as proved by a co-localization of fluorescent markers entrapped inside liposomes and incorporated into the liposomal membrane. After 2 hours liposomes had slowly migrating towards cell nuclei. Liposomes had completely disintegrated with their inner marker released by approximately 9 hours. TAT peptide-liposomes were made slightly cationic by adding up to 10 mol %. of a cationic lipid (DOTAP). These slightly cationic liposomes were non-toxic towards cells, formed firm complexes with DNA (plasmid encoding for the formation of the Green Fluorescent Protein), and efficiently transfected a variety of cells. TAT peptide-liposomes can be considered as promising carriers for the non-endocytotic intracellular delivery of drugs and DNA.
Torchilin
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Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA. v.torchilin@neu.edu
Levchenko
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D000818:Animals; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000378:metabolism; D002412:Cations; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014161:Transduction, Genetic
D002352:Carrier Proteins; D002412:Cations; D004337:Drug Carriers; D015696:Gene Products, tat; D008081:Liposomes; D010455:Peptides; D011994:Recombinant Proteins; D004247:DNA