When polymer chains are grafted to a polymer backbone, a molecular polymer brush is formed. This polymer architecture is also referred to as a polymer bottlebrush. The close proximity of polymer chains within one brush molecule endow such molecular brushes with new properties that are distinctly different from linear polymer counterparts. In many ways, brush polymers are basically one giant polymer construct that comprises nanoscale dimensions. This nanoparticle character has prompted the increasing use of polymer brushes in the areas of polymer self-assembly, nanomedicine and template chemistry.

Our group has extensive expertise in the synthesis and application of molecular polymer brushes.

Please refer to the following review articles as an introduction to this area of research.

• M. Müllner Molecular Polymer Bottlebrushes in Nanomedicine: Therapeutic and Diagnostic Applications Chem. Commun. 2022, 58, 5683-5716.
• T. Pelras, et al. Synthesis and applications of compartmentalised molecular polymer brushes. Angew. Chem. Int. Ed. 2018, 57, 6982-6994.
• M. Müllner et al. Cylindrical Polymer Brushes – Anisotropic Building Blocks, Unimolecular Templates and Particulate Nanocarriers. Polymer 2016, 98, 389-401.
• M. Müllner Molecular Polymer Brushes in Nanomedicine. Macromol. Chem. Phys. 2016, 207 , 2209-2222.

Nature’s countless examples of multi-functional advanced materials are often achieved by bottom-up self-assembly of organic and inorganic building blocks. We are interested in progressing that synthesis of compartmentalised polymeric building blocks that will ultimately allow for a bottom-up construction of superstructures through polymer-polymer and inter-particle associations. The use of block copolymers in self-assembly (solution or bulk) has come a long way. With it came a in-depth understanding about what governs self-assembly and how can it be manipulated.

We are interested in adding new building blocks to the mix. Using molecular brushes in solution and bulk self-assembly achieves faster self-assembly kinetics and provides access to larger domain spacing. This has led to the development of new surfactants or photonic coatings. We use brush building blocks that are compartmentalised into domains (e.g. block-type or core-shell).

Brushes with a core-shell structure can act as cylindrical template to assemble polymers along the brush backbone. Using interpolyelectrolyte complexation we could build uniformly segregated nanowires featuring stacked discs along the brush long axis (see image).

At the same time, we used block-type brushes as a high molecular weight analogue to linear block copolymers and explored their self-assembly in emulsion droplets. Again, we were able to generate stacked lamellae/discs, but this time in the shape of an ellipsoid.

Currently, we explore the above methods further to produce nano-scale discs for biomedical applications.

Selected references:

• T. Pelras et al. Cylindrical Zwitterionic Particles via Interpolyelectrolyte Complexation on Molecular Polymer Brushes. Macromol. Rapid Commun. 2020, 42, 2000401.

  T. Pelras et al. Polymer Nanowires with Highly Precise Internal Morphology and Topography. J. Am. Chem. Soc. 2018, 140, 12736-12740.
• A. Steinhaus et al. Self-assembly of diblock molecular polymer brushes in the spherical confinement of nanoemulsion droplets. Macromol. Rapid Commun. 2018, 39, 1800177.
• A. Steinhaus et al. Confinement Assembly of ABC Triblock Terpolymers for the High-Yield Synthesis of Janus Nanorings. ACS Nano 2019, 13, 6269-6278.

Polymer- and nanoparticle-based delivery systems are expected to overcome limitations of traditional drug delivery strategies. While many strides have been made in drug carrier design, the superficial penetration of tumours by nanoparticles remains a key hurdle to treatment success.

In this context, we are mapping a structure-function-property relationship using our molecular polymer brush nanomaterials. We were one of the first teams to establish that polymer brush-based nanoparticles are promising in nanomedicine applications. Since then, we have better understood our nanoparticle platform and are using our controlled synthesis methods to screen for ideal nanoparticle design parameters with the ultimate goal of improving tissue and tumour penetration of future polymer nanomedicines. Along the way, we have already established that our materials can deliver cytotoxic drugs and accumulate in tumours. Intriguingly, we can use nanoparticle shape, aspect ratio, amphiphilicity and stiffness to influence the how our material interacts with the biological domain. Most recently, we showed that subtle changes to brush stiffness affect their intracellular fate, providing possible mechanical means to control treatment outcomes in the future.

Selected references:

• P. Ramamurthi, et al. Tuning the Hydrophilic – Hydrophobic Balance of Molecular Polymer Bottlebrushes Enhances their Tumor Homing Properties. Adv. Healthcare Mater. 2022, 2200163
• N. Niederberger et al. Stiffness-Dependent Intracellular Location of Cylindrical Polymer Brushes. Macromol. Rapid Commun. 2021, 42, 2100138.
  
• M. Müllner et al. Aspect-ratio-dependent interaction of molecular polymer brushes and multicellular tumour spheroids. Polym. Chem. 2018, 25, 3461-3465.
• T. Pelras et al. A 'Grafting from' Approach to Polymer Nanorods for pH-Triggered Intracellular Drug Delivery. Polymer 2017 ,112, 244-251.
• X. Chen et al. Shape-Dependent Activation of Cytokine Secretion by Polymer Capsules in Human Monocyte-Derived Macrophages. Biomacromol. 2016, 17, 1205-1212.
  
• M. Müllner et al. Passive Tumour Targeting and Extravasation of Cylindrical Polymer Brushes in Mouse Xenografts. Chem. Commun. 2016, 52, 9121-9124.
• M. Müllner et al. Size and rigidity of cylindrical polymer brushes dictate long circulating properties in vivo. ACS Nano 2015, 9, 1294-1304.

We have developed several synthetic approaches to produce highly uniform hybrid materials by using innovative molecular scaffolds, in situ nanostructuring or by applying typical template chemistry. Polymers and polymer architectures offer a powerful platform as they allow for precise tailoring of structuring domains at the nanoscale.

We have broaden our materials design to also include renewable resources, such as cellulose or tannins. Using tannic acid, we developed a new hydrogel-based templating method to produce porous nanocrystalline semiconducting materials and tested their performance as lithium-ion battery electrodes. We are now exploring this method to prepare mixed metal oxides for photocatalytic processes.

Selected references:

• Y.T. Cheng et al. Polymer Brush-Grafted Cellulose Nanocrystals for the Synthesis of Porous Carbon-Coated Titania Nanocomposites. Polym. Chem. 2023, accepted.
• Y.T. Cheng et al. Tunable Polymer Nanoreactors from RAFT PISA: Fabrication of Nanostructured Carbon-Coated Anatase as Battery Anode Materials with Variable Morphology and Porosity. ACS Appl. Mater. Interfaces 2023, 15, 12261-12272.
• M. Schottle et al. Integrated Polyphenol-Based Hydrogel Templating Method for Functional and Structured Oxidic Nanomaterials. Chem. Mater. 2020, 32, 4716-4723.
• O. McRae et al. Block Copolymer-Directed Synthesis of Porous Anatase for Lithium-Ion Battery Electrodes. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1890-1896.
  
• M. Morits et al. Polymer brush guided templating on well-defined rod-like cellulose nanocrystals. Polym. Chem. 2018, 13, 1650-1657.
  

Photochemistry is a rapidly growing research area again. Over the past five years, many radical polymerisation methods have been endowed with spatio-temporal control via the incorporation of light, and photoredox catalysts more specifically. In this context, we have developed light-driven RAFT polymerisations using a heterogenous photocatalyst (e.g. bismuth oxide). Our seminal work showed that bismuth oxide is powerful in polymer synthesis, while at the same time being recyclable and applicable in both organic and aqueous systems. Similarly, we can use semiconductor catalysts to generate peptide-polymer hybrids as well as unconventional polymer architectures such as cyclic and step-growth multiblock copolymers.

Selected references:

• K. Hakobyan et al. Visible Light‐Driven MADIX Polymerisation via a Reusable, Low‐Cost and Non‐Toxic Bismuth Oxide Photocatalyst. Angew. Chem. Int. Ed. 2019, 58, 1828-1832.
• K. Hakobyan et al. Activating ATRP Initiators to Incorporate End-Group Modularity into Photo-RAFT Polymerization. Macromolecules 2020, 53, 10357–10365.
• M. Müllner et al. Surface-initiated polymerization within mesoporous silica spheres for the modular design of charge-neutral polymer particles. Langmuir 2014, 30 , 6286-6293.
• K. Hakobyan et al. RAFT without an “R-Group”: From Asymmetric Homo-telechelics to Multiblock Step-Growth and Cyclic Block Copolymers. Macromolecules 2021, 54, 7732-7742.
• T. Gegenhuber et al. Molecular polymer brushes via ring opening metathesis polymerization made from cleavable RAFT macromonomers. Macromol. Chem. Phys. 2021, 222, 2100077.