On Thursday, June 2nd, 2016 at 13:00 o'clock in Freie Universität Berlin, seminar room in Fabeckstr. 34-36, 14195 Berlin (Dahlem,
Prof. Stavroula Sofou, Ph.D. (Departments of Biomedical Engineering, and Chemical and Biochemical Engineering, Rutgers University, USA)
will speak on "Sticky patches on lipid nanoparticles generate binding geometries that enable effective targeting of otherwise untargetable cancers”.
The majority of breast cancer patients (70%) have tumors designated as 'HER2-negative' (<1+ HER2-expression evaluated by immunohistochemistry or < 200,000 HER2-copies per cell). For these patients there are no targeted therapeutic options utilizing the HER2 receptor. The ability of uniformly targeted nanoparticles for specific targeting stops to hold on cancer cells expressing less than 200,000 copies of HER2 per cell or less than two receptors per nanoparticle's projected area. This geometry corresponds to the limit of multivalent interactions (avidity) loosely defined as multiple contacts between neighboring same-cell receptors with ligands from a single nanoparticle. An alternative therapeutic approach would be needed, therefore, to enable selective targeting and effective killing of cancer cells with low HER2 expression.
Towards this goal we designed targeted lipid nanoparticles that contain HER2-targeting ligands densely conjugated within sticky patches. Sticky patches are phase-separated raft-like lipid-domains of high local multivalency which is induced by preferential partitioning of peptide-functionalized lipids. To enable selectivity in binding, sticky patches are exclusively triggered to form in mildly acidic environments matching the tumor interstitium.
We show that lipid nanoparticles with sticky patches selectively associate with and kill triple negative breast cancer cells while do not affect cardiomyocytes and breast normal cells (both expressing the same targeted receptors at considerably lower but not insignificant levels). These findings support the potential of these new binding geometries to enable targeting of otherwise untargetable cancers.