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

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°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.

Keywords::

• Thermosensitive liposomes
• immunoliposomes
• breast cancer
• Her-2
• C-erbB-2
• trastuzumab

Acknowledgements

We thank Dr Richard Kullberg for his critical review of the manuscript, and Dr Carol Jones for her support. Thanks to Dr Max Rabinowitz at Alaska Oncology and Hematology for the generous donation of trastuzumab. This work was funded by grants from the Alaska Run for Women, Alaska Men's Run, and the WWAMI program at the University of Alaska Anchorage.

Declaration of interest: The authors report no conflicts of interest.