The conjugation of proteins, peptides or other biomolecules to polymers has been an active research field for many years now.1, 2An alternative pathway could be the reaction between boronic acids and alcohols. Boronic acids can undergo reactions with a range of compounds, most notably with 1, 2-dihydroxyl functionalities, with high affinity via reversible boronate esters formation. It is possibly one of the strongest single-pair reversible functional group interactions in an aqueous environment and it has already been utilised for various biomedical applications.3 These encouraging results inspired us to test this chemistry for conjugation of biomolecules to the surface of micelles. Particularly appealing is the potentially reversible nature of the boronic acid ester as a tool to detect pH changes. Aim is to explore borate esters as an efficient tool for bioconjugation, but also to investigate the stability of the complex at various pH values. We therefore developed a RAFT (reversible addition fragmentation chain transfer) agent4 based on dopamine, which is known to have a high affinity towards boronic acid. Subsequent polymerization led to blockcopolymer that were conjugated to platinum drugs in the core. Folic acid was attached to the surface by boronic acids.5 Although the complex is pH-responsive, it is reasonably stable under physiological condition. However, the susceptivity of the catechol functionality to oxidation and complex formation result in the disassociation of the boronic complex during apoptosis where increased oxidation and Ca2+influx could potentially lead to the liberation of the boronic acid, thus it can be used to monitor the onset of apoptosis. 1. Grover, G. N.; Maynard, H. D. Current Opinion in Chemical Biology 2010, 14, (6), 818-827.2. Le Droumaguet, B.; Nicolas, J. Polym. Chem. 2010, 1, (5), 563-598.3. Cambre, J. N.; Sumerlin, B. S. Polymer 2011, 52, (21), 4631-4643.4. Gregory, A.; Stenzel, M. H. Progress in Polymer Science 2012, 37, (1), 38-105.5. Scarano, W.; Duong, H. T. T.; Lu, H.; De Souza, P. L.; Stenzel, M. H. Biomacromolecules 2013, 14, (4), 962-975.

Boronic esters as a tool for bioconjugation to deliver platinum drug loaded micelles

248th National Meeting (2014)

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