A two-component drug delivery system using Her-2-targeting thermosensitive liposomes.
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.
Kullberg
Max
M
Biomedical Program, University of Alaska, Anchorage, AK 99508, USA. afmpk@uaa.alaska.edu
Mann
Kristine
K
Owens
Jesse Lee
JL
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism; D005240:Feasibility Studies; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012235:Rhodamines; D013696:Temperature; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D018719:Erb-b2 Receptor Tyrosine Kinases; D012235:Rhodamines; D000068878:Trastuzumab; C007740:fluorexon