RSA CE&C 2015-2021 Group descriptions

44 2. Compartments with life-like features Different life-like features have been incorporated in soft matter systems. In this regard, we have developed self-regulating polymeric nanoreactors. Polymersomes were created with a pH-responsive shell. Inside the polymersome, the enzyme urease and a second enzyme were encapsulated. Through exposure to acidic urea buffer, the polymer membrane was swollen and therefore permeable to the substrate molecules for both enzymes. Urease, converting urea into ammonia, changed the pH back to high values, thereby closing the membrane again. This transient breathing behavior enables the regulation of a process independently of the process components, which is an important additional feature for the development of life-like materials. 6,7 A second major activity in this research theme is the construction of active systems (i.e., nanomotors). We have been able to create bowl-shaped polymer vesicles, or stomatocytes (see section 4), which were loaded in their nanocavity with catalytic cargo. These catalytically active stomatocytes were shown to function as autonomous moving objects via the catalytic dissipation of chemical fuels. 8 To mimic biological systems more closely, we incorporated a six-enzyme metabolic pathway mimicking the process of homeostasis. 9 We have also been able to induce motility in our coacervate protocell platform (see section 1). By conjugating the enzyme catalase to the fluidic membrane, stochastic processes resulted in transient asymmetric positioning of the enzyme which led to enhanced diffusion of the entire protocell. 10 3. Stimulus-responsive nanoparticles in nanomedicine Using a protein engineering approach, we have been able to construct protein particles out of stimulus-responsive polypeptides. These polypeptides were derived from elastin- like polypeptides and the capsid protein of the plant virus CCMV. The responsiveness could be used to modularly assemble different components in well-defined biologically active particles, which could be used, for example, for photodynamic therapy (PDT) in which a photosensitizer is activated by irradiation to locally produce oxygen radicals. 11, 12 PDT was also the focus of nanotherapeutics based on nanogels and peptides which were assessed in vivo. The former type of particle was composed of a polymer nanogel to which a photosensitizer was conjugated. Inside, the gel enzyme-decorated nanoparticles of MnO 2 were enclosed. These particles accumulated in the tumor tissue, increased oxygen levels and made the tumors more susceptible to oxygen radical damage. This led to a much-improved therapeutic outcome. 13,14 4. Shape effects on biological activity Kinetic control has been used to construct polymersomes with non-spherical shapes. Polymersomes are traditionally formed by the addition of water to an organic solution of a block copolymer. An excess of organic solvent then has to be removed from the solution. We have pioneered the usage of dialysis, which results in a shape change process during the removal of organic solvent. Based on a thorough mechanistic understanding, we have been able to create discs, bowl-shaped structures called stomatocytes, and cucurbit-like and tubular polymersomes, including from biodegradable block copolymers. 15-18 The unique shape control has been used to create nanosized red blood cells capable of both oxygen transport and PDT. 19 Furthermore, the integration of aggregation-induced emission units in the polymer membrane has provided us with a class of polymersomes with excellent shape change and therapeutic features. 20