Qualitative and quantitative effects of molecular ligands on targeting cancer cells with nanosystems

Targeting diseased cells with nanosystems remains a major challenge for biomedical applications of nanotechnology, where cancer theranosis is the most promising domain. In order to improve cancer cell targeting, the common strategy consists in ingeneering the nanosystem surface with various molecular ligands, from small molecules to antibodies, intended to favor its interaction with targeted cells. In the present talk wesuggest to overview some representative data from literature and from our experience with different types of nansystems: nanoliposomes and hybrid nanoparticles made of an inorganic core and organic shell. In our study, we will compare nanosystems having similar size and polymeric coating in polethylene glycol (PEG), decorated with similar biological targetting ligands (folic acid, cell-penetrating peptides, antibody fragments). All the nanosystems were carefully characterized in terms of their physico-chemical poperties prior to study their interaction with cancer cells in vitro (MCF-7, MDA-MB-231, MDA-MB-435, HeLa, etc). The comparison of ligand free PEGylated (control) and ligand carrying PEGylated nanosystems will be made to establish a possible structure-activity relationship. We will discuss on the data demonstrating that molecular ligands affect nanosystem-cell interactions in both quantitative (intracellular accumulation) and qualitative (nanosystem internalisation, subcellular localisation/interaction and drug delivery) manner. We will also describe innovative analytical methodology which allows to reach the relevant and complete understanding of the nanosystem-cell interactions in vitro, in particular on the intracellular fate of the nanosystems and of their cargo.