Étude du comportement d'ADN en solution et aux interfaces et le rôle de la dynamique micellaire et la rhéologie dans la libération contrôlée de médicaments

摘要

Nowadays, the target for reaching a greater efficiency in DNA compaction processes, the innovation ofDNA sensors development and the study of changes in the interfacial properties generated between metalsurfaces and DNA molecules has become an area of great interest in bioengineering. This section of thethesis proposes the coupling of rheological, electrochemical and optical techniques to perform a detailedstudy of DNA molecules behavior in the bulk state of the solution and at the interface with two differentmetallic surfaces, as a function of parameters such as temperature, DNA concentration and electricpotential. Firstly, the rheological behavior of DNA/buffer solutions, as well as the evidence of the criticalconcentrations (C★ and Ce) is discussed from simple steady state and oscillatory dynamic shearexperiments. After studying DNA solutions properties, electrochemical and optical techniques are used toidentify structural changes in Au/DNA and Pt/DNA interfaces and to describe the arrangement of DNAchains in the electrochemical double-layer as a function of concentration and within each characteristicregime, i.e. dilute and semi-dilute regimes. The obtained response trough Electrochemical ImpedanceSpectroscospy (EIS), Modulation Interfacial of the Capacitance (MIC) and Surface Plasmon Resonance(SPR) techniques reflects an adsorption process of DNA molecules taking place onto the metal surfaces.Finally, by selecting DNA concentrations in the dilute regime, we studied the formation of chitosan-DNAnanoparticles with defined stoichiometry for gene transfer.The specific delivery of active ingredients, known as vectorization, has actually become a greatchallenge in therapeutic research. This process has been used to control the distribution of activeingredients such as proteins, genes for gene therapy and drugs, to a target by associating it with avector. Molecules for chemotherapy are frequently hydrophobic and require vectorization to betransported to the target cell. In this section of the thesis, we look up to understand the collectiveexchange dynamics (fusion and fission) between amphiphilic block copolymer micelles at the equilibriumand out of the equilibrium, and the exchange dynamics between these micelles (representing vectors)and the simplest model of cells (liposomes). We used a fluorescent technique with hydrophobic pyrenederivative to probe the fusion and fission of micelles at equilibrium. After characterizing amphiphilicblock copolymers structure and studying their dynamics in and out of equilibrium, we proposed a timescan fluorescence technique to quantify the collective vectorization dynamics between amphiphilic blockcopolymer micelles and liposomes. The effect of the variation of several parameters such as liposomeconcentration and a chitosan adsorption were investigated in order to control the vectorizationdynamics between these vectors and cells models.