Our goal is to develop a model for the binding, internalization, and tumor-killing dynamics of liposome-enclosed doxorubicin targeted to cancer cells and develop design principles for creating more effective therapeutics.

Liposomes with internal small molecule chemotherapeutics and external ligands specific to cancer-associated cell surface receptors are a promising strategy for next generation anti-cancer therapeutics. The ligands facilitate tight, specific interactions with targeted cancer cells, and upon internalization, deliver their toxic payload locally. In particular, we study liposomal doxorubicin with attached F3 ligand specific to nucleolin overexpressing cancer cells. We build a kinetic model to capture this process and parameterize it with binding, internalization, and cell killing assays in five cell lines. We study the similarities and differences between the liposome's effect on the cell lines, manifesting as model parameter differences in accessible surface area/receptor density, liposome internalization and processing rate, and cell-killing activity. This enables the examination of tunable aspects of drug design like ligand strength and density and further general studies of potency and off-target/side effects.In collaboration with Prof. João Nuno Moreira, University of Coimbra, Portugal

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Rui Lopes