Protein-and Peptide-functionalized nanovectors for anticancer theranosis

Among biomedical applications of nanotechnology, cancer theranosis (therapy and diagnosis) is one of the most promising domains. In order to improve the nanosystems biocompatibility, they are usually coated with neutral biocompatible polymers like polethylene glycol (PEG). For cancer cell enhanced and specific targeting with injectable nanosystems, the common strategy consists in engeneering the nanosystem surface with various biologically relevant ligands (from small molecules to antibodies). Peptides have several interesting properties as ligands for anticancer nanomedicine. In the present talk, we will expose our recently developed PEGylated and peptide-functionalized injectable nanovectors based on nanoliposomes or on superparamagnetic iron oxides (SPIONs). Their PEG polymeric coating was covalently coupled to (i) membranotropic cell-penetrating peptides gH625[1] or to (ii) scFv fragments of antibody trastuzumab, specific of HER2 positive breast cancers[2]. Once synthetized, the novel nanovectors were carefully characterized in order to establish their physicochemical properties (size and zeta potential in a wide range of pH, chemical composition and structure). Then, the nanovectors interaction with cancer cells has been studied in vitro, on various cancer cell lines, overexpressing or not specific receptors, thus playing a role of positive or negative controls. By comparing ligand-free PEGylated (control) and ligand carrying PEGylated nanovectors we attempt to establish a possible role of the ligands. As we will show, the ligands are able to affect nanosystemcell interactions both quantitatively (intracellular accumulation) and qualitatively (nanosystem internalisation, subcellular localisation/interaction and drug delivery). We will also present some methodological developments we made to shed a light on the nanosystem-cell interactions, in particular on the intracellular fate of the nanosystems and of the drugs they deliver