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Résumé |
"A biophysicist approach to targeted drug delivery to cancer cells" \\
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One of the major challenges in drug delivery is the ability to target exclusively sick cells
without interacting with healthy cells. This is particularly important for cancer drug
delivery. In this presentation we show how we can take advantage of the modifications
that occur on the plasma membrane of cancer cells to target surface modified
nanoparticles. The basic idea is to take advantage of the over-expressed receptors and the
different lipid composition of the plasma membrane in (some) cancer cells. To this end
we show, as a proof of concept, how modifying the surface of the nanoparticles with
binary mixtures of short polymers can increase the binding to the cells by orders of
magnitude. One of the polymers in the mixture is aimed at protecting the nanoparticle
and the other is a polybase with a functional ligand as its end-group that specific targets
the overexpressed receptors in the cancer cell. We show how the combination of
electrostatic interactions, specific binding, acid-base equilibrium and molecular
organization in the nanoparticle and on the lipid layer provides for a non-trivial
synergetic effect with highly improved binding capabilities. We will show how the
approach of the nanoparticle to the lipid layer results in a highly inhomogeneous
segregation of lipids in the cell membrane and of polymers in the nanoparticle. The
molecular segregation can be used as a tool not only for drug delivery but also for
molecular recognition of surface domains. The complex non-additive interplay between
chemical reactions and physical interactions in highly inhomogeneous environments that
we predict points out to the need to develop novel intuition for these strongly coupled
systems. For example, we show how the addition of two repulsive interactions can lead to
a combined attraction. The relevance for the fundamental understanding of processes in
cell biology as well as in the design of responsive materials will be discussed. |
