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J Drug Target. 2009 Feb;17(2):98-107. doi: 10.1080/10611860802471562 .

A two-component drug delivery system using Her-2-targeting thermosensitive liposomes.

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  • 1Biomedical Program, University of Alaska, Anchorage, AK 99508, USA. afmpk@uaa.alaska.edu

Abstract

We report on a new method for enhancing the specificity of drug delivery for tumor cells, using thermosensitive immunoliposomes. The liposomes are conjugated to the antibody trastuzumab (Herceptin), which targets the human epidermal growth factor receptor 2 (Her-2), a cell membrane receptor overexpressed in many human cancers. Being thermosensitive, the liposomes only release their contents when heated slightly above body temperature, allowing for the possibility of tissue targeting through localized hyperthermia. Using self-quenching calcein, we demonstrate the release of liposome contents into cell endosomes after brief heating to 42 degrees C. To further increase targeting specificity, we incorporate the concept of a two-component delivery system that requires the interaction of two different liposomes within the same endosome for cytoplasmic delivery. Experimental evaluation of the technique using fluorescently labeled liposomes shows that a two-component delivery system, combined with intracellular disruption of liposomes by hyperthermia, significantly increases specificity for Her-2-overexpressing tumor cells.

PMID:
19089689
[PubMed - indexed for MEDLINE]
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