Fine-Tuning Biodegradable Polymersome Membrane Permeability by the use of a Fine-tuned Polypeptoid Composition

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Mimicking nature has always been a driving force in science. With research coming down to the molecular level, mimicking cells and cellular compartments came into focus and was established as synthetic biology. Since the formation of separate compartments for specific tasks is essential in the formation of living cells, rebuilding such compartments from the scratch is of high scientific interest. In order to do so form totally synthetic compartments, amphiphilic block copolymers have proven to be a feasible way to produce artificial vesicles, which are called polymersomes. Until now, the polymers used are mainly non-biodegradable. When it comes to a biological application, however, these polymers should be totally biodegradable in order to rule out toxic side-effects also in the long term. In this project, polypeptide-like polymers, the so-called polypeptoids are to be used. These macromolecules are chemically very similar to their biological counterpart and are built up of biologically cleavable amide bonds. Another advantage of these polymers is their simple synthesis. According to literature a variety of monomers with different functionalities can be accessed easily within 3 steps. In addition, the polymer itself is also readily accessible once the monomers are available. Hence, polypeptoids are a suitable choice for creating polymersomes which are fully biologically compatible. Once the monomers are available, different polymers need to be synthesized to see, which ones form the desired structures and are feasible for further studies. This has to be done for polymers for 2 separate applications, the drug-delivery-system (DDS) and the nanoreactors. If designed for DDS, the polymersomes ought to disintegrate once they reach their final destination, but stay intact beforehand. The cargo is the securely stowed in the polymersomes at first at efficiently released at its destination. However, in order to reach a specific destination only, the polymersomes need to be equipped with a functionalized surface for them to be recognized be certain cell types only . Due to the chemical structure of the polypeptoids, such modified initiators are readily accessible. Apart from that, surface functionalization with dyes is important for imaging reasons for polymersomes designed for DDS as well as nanoreactors. The latter ones though need to be stable at all conditions and should not release their enclosed catalyst (e.g. an enzyme) into the outside matrix at any time. In contrast, the polymersome membrane is now to gate and control the activity of the catalyst. Hence, it is the goal of this project to create polymersomes out of a flexible polypeptoid system, which can be fine-tuned specifically for different applications, DDS as well as nanoreactors, separately.