Seminar: Dr Markus Müllner - Cylindrical polymer brush nanoparticles as molecular scaffolds and prototype polymer nanomedicines

Thursday, 23 February 2017 - 12:00pm – Thursday, 23 February 2017 - 1:00pm  |  Law G23

Speaker: Dr Markus Müllner

A rational and application-focused design of materials is expected to overcome many limitations in current materials and biomedical sciences. The possibility to precisely engineer at the nanoscale enables the synthesis of materials with tailored chemical composition and physicochemical properties. Advances in synthetic polymer science have further nourished the fabrication of highly functional and stimuli-responsive polymeric materials. Within this space, the modular synthesis of cylindrical polymer brushes (CPBs) provides access to a new class of materials that are extremely powerful in molecular templating and which emerge as promising delivery vehicles in nanomedicine.1-3 CPBs, or molecular brushes, are one-dimensional nanostructures consisting of polymer chains densely tethered onto a polymer backbone. The grafting density of polymer chains eventually becomes so high that the chains become crowded and stretched, leading to the typical cylindrical shape of CPBs. Due to the shape-persistent nature, the extraordinary spatial dimensions and the tuneable architecture of CPBs, new opportunities of fabricating bottom-up nanomaterials have been created, providing access to nanostructures that are difficult to yield from linear polymers. Due to their cylindrical shape and multiple individually separated compartments, CPBs are able to be applied as delivery vehicles or template materials. To date, only a small number of in vitro reports have described potential biomedical applications of cylindrical polymer particles, showing composition-dependent cellular interactions and strategies to release drugs to kill cancer cells.4


Recently, we initiated studies to investigate the in vivo behaviour of CPBs and to evaluate the impact of changes to length and rigidity on in vivo clearance, distribution and persistence.5 Fine control over particle properties enabled an initial investigation of the impact of size, aspect ratio and rigidity on in vivo pharmacokinetic behavior in a rat model. The impact of changes to aspect ratio on accumulation in xenograft mice models have further revealed that nanoparticle shape my hold benefits over spherical counterparts.6 In our current research, we have continued to develop CPBs as a drug delivery platform for cytotoxic cargo release and deep tumour penetration.


In this seminar, I will discuss the use of CPBs as molecular scaffolds and prototype nanomedicines.

REFERENCES
1. Verduzco, R.; Li, X.; Pesek, S. L.; Stein, G. E. Chem. Soc. Rev. 2015, 44, 2405-2420.
2. Rzayev, J. ACS Macro Letters 2012, 1, 1146-1149.
3. Müllner, M.; Müller, A. H. E. Polymer 2016, 98, 389-401.
4. Müllner, M. Macromol. Chem. Phys. 2016, 217, 2209-2222.
5. Müllner, M.; Dodds, S. J.; Nguyen, T.-H.; Senyschyn, D.; Porter, C. J. H.; Boyd, B. J.; Caruso, F. ACS Nano 2015, 9, 1294-1304.
6. Müllner, M.; Mehta, D.; Nowell, C. J.; Porter, C. J. H. Chem. Comm. 2016, 52, 9121-9124.