Encapsulation of viruses and magnetic nanoparticles

The present proposal generates gels and capsules based on homo- and block copolymers for the encapsulation of magnetic nanoparticles together with viruses, thus enhancing the effectiveness of the transfection process. Three different types of structures will be prepared : (a) micro-gels built from short polymeric molecules bearing supramolecular donor/acceptor moieties (b) polymersomes built from block copolymers and (c) lipid bilayer vesicles. The respective homo- and block copolymers will be synthesized by living polymerization methods, which allows a postmodification with the necessary hydrogen-bonding structures by subsequent chemical methods. Release mechanisms will be included into the polymeric structures, relying on temperature-, pH-, and glucose sensitive stimuli. Magnetic nanoparticles will be generated and either linked onto the surface of the viruses or serve as anchoring points for enzymes able to trigger the subsequent release of the viruses at the site of medical-action. The viruses (generated by the cooperation-group of Prof. Günzburg) will be encapsulated together with the magnetic particles into the polymeric shells / gels and their magnetic behavior studied in vitro as well as in vivo, aiming at the development of an efficient new gene-therapeutic system.

The site directed delivery of pharmacologically active substances is still an important issue in medicinal chemistry. Besides conventional pharmaceuticals (such as small molecular weight drugs comprised of organic molecules with molecular weights below 1000 Da) the specific formulation and application of peptides, proteins, DNA and whole viruses are a major point of interest for treating diseases in a nondestructive and effective manner. The project was started with investigations on supramolecular gels, held together via hydrogen bonding systems. A strong temperature-sensitivity of a synthetically deisgned gel based on hydrophobic and hydrophilic polymers was observed due to the reversibility of the hydrogen bonding moieties. Magnetic nanoparticles and functionalized dyes could be incorporated into the gel, generating a supramolecular, magnetic gel for the first time. This approach was then extended by including a thermosensitive polymer (PNIPAM) into the gel, thus inducing stronger thermal properties into the gel-structure. A second approach was based on the use vesicles and polymersomes, focussing on the stabilization of the outer membrane structure by silicification processes and the subsequent incorporation of (superparamagnetic) nanoparticles). Thus new capsules with defined shells of silica around a liposome or polymersomes, together with included nanoparticles could be obtained. Furthermore, a human-rhinovirus was encapsulated by fully preserving its function and infectivity. The researched approach allows to generate included active viruses into preformed silica shells, together with magnetic nanoparticles able to guide the location of the virus.