Self-assembly of Responsive Polymer/Peptide-based Micelles for Biomedical Applications Studied by State-of-the-art Scattering Techniques

I dette prosjektet anvendes "intelligente" kjedemolekyler (blokk-kopolymerer) bestående av blokker, som har forskjellige kjemisk sammensetning. Det ?intelligente? ved disse polymerer er, at de responderer aktivt og reversibelt på ydre stimuli (f.eks. temp eraturer, pH, lys) og danner nano-strukturer. Vi kan ved stimuli eksempelvis åpne og lukke nano-kapsler, som kan brukes til biomedisinske formål. Ved å utføre hurtige tidsoppløste Røntgen- og neutronsprednings forsøk, som er mulig ved moderne synkrotron- og spallationskilder, vil vi kunne se direkte, hvordan partiklene dannes på nanometer- og millisekundskala, hvordan medisinen innkapsles, og hvordan medisinen frigis igjen etter en ytre stimulus. I dette grunnleggende studium vil vi altså oppnå ny viten g jennom å å lage en ?nano-movie? av selv-associerede nano-kapsler og dermed få et innblikk i, hvordan vi best kan utnytte naturens egne metoder til å danne funksjonelle partikler til nanoteknologiske og biomedisinske formål."

Nano-technology and biomedical applications require an increased control of the preparation and functionalization of nano-particles and nano-assemblies. Here we propose a chemical engineering approach to use intelligent responsive polymeric materials and self-assembly to create functional nano-particles and nano-assemblies for controlled solubilisation and release. These could be used as nano-carrier systems for drugs with predetermined structural and dynamic properties. We propose a novel strategy contro lling nano-encapsulation and solubilization by both thermodynamical and kinetic control. The idea is based on taking advantage of responsive polymers that change their solubility with external parameters (pH, light, temperature ) and rapidly co-precipitat e these with drug molecules, effectively creating stable but controllable nano-carriers for encapsulation. The strategy involves using tuneable well-defined model systems, starting from simple synthetic block copolymers and then gradually increasing the c omplexity towards biologically functional materials where one block is replaced by a peptide block. In order to study the detailed structural properties and characterize the spatial repartition of drug molecules, we will apply small-angle neutron and x-ra y scattering techniques combined with careful theoretical modeling. The co-assembly processes will be monitored in situ by applying state-of-the-art time-resolved small angle scattering with millisecond resolution. This will be combined with pharmaceutic al studies of release kinetics (in vitro and in animal models). This project is expected to not only give a significant advancement in the understanding of self-assemblies, but also a far-reaching methodology for better use of polymer systems and scatt ering techniques in the areas of pharmacy, biomedicine and nano-technology.