Polymers for Health 5
Drug carriers inspired by nature: Nanoparticles with sugar antennas
Prof Martina Stenzel
Carbohydrates have become a hot topic for research within the scientific community. This is due to the myriad of biological communication events, including: cellular recognition, inflammation, signal transmission and infection of pathogens displayed by them. In the treatment of diseases, such as cancer, cytotoxic chemotherapy or radiotherapy can be life threatening as the therapeutics used are normally not site-specific. To improve the distribution of drugs in a biological system, the use of ligand (e.g. carbohydrate and peptide targeted therapeutics for the recognition of malignant cells), could be an important step towards the improved treatment of cancer and other diseases.
Moreover, many studies have shown that lectins on cell surfaces mediate cell-cell interactions by combining with complementary carbohydrates; in other words, the incorporation of ligands such as carbohydrates or other targeting moieties could result in increased cellular uptake via receptor-endocytosis.
Synthesis of glycopolymers has been one of our core-activities over the last few years. The polymers are prepared wither by direct RAFT polymerization of glycomonomers or by post-functionalization of active polymers. The polymer may have either have linear architectures, star-like structures or might even self-assemble into micelles. The type of polymer structure was found to influence binding with lectins. For example, a micelle with the sugars bound to the surface by dendrimers was observed to be more efficient than a traditional glycopolymer micelle.
Our work has two aspects: theoretical understanding of the relationship between glycopolymer architecture and the rate of lectin binding, but we also look for very practical aspects for the use of glycopolymers to deliver vaccines or to treat cancer. Nanoparticles coated with sugars have a preference to enter only specific tumour cells, while others remained almost unaffected.
- Ting, S. R. S.; Gregory, A. M.; Stenzel, M. H., Polygalactose Containing Nanocages: The RAFT Process for the Synthesis of Hollow Sugar Balls. Biomacromolecules 2009, 10, 342-352.
- Ting, S. R. S.; Chen, G. J.; Stenzel, M. H., Synthesis of glycopolymers and their multivalent recognitions with lectins. Polymer Chemistry 2010, 1, 1392-1412. (review article)
- Chen, G. J.; Amajjahe, S.; Stenzel, M. H., Synthesis of thiol-linked neoglycopolymers and thermo-responsive glycomicelles as potential drug carrier. Chemical Communications 2009, 1198-1200.
- Chen, Y.; Chen, G. J.; Stenzel, M. H., Synthesis and Lectin Recognition of Glyco Star Polymers Prepared by "Clicking" Thiocarbohydrates onto a Reactive Scaffold. Macromolecules 2010, 43, 8109-8114.
- Kumar, J.; Bousquet, A.; Stenzel, M. H., Thiol-alkyne Chemistry for the Preparation of Micelles with Glycopolymer Corona: Dendritic Surfaces versus Linear Glycopolymer in Their Ability to Bind to Lectins. Macromolecular Rapid Communications 2011, 32, 1620-1626.