Synthesis and characterization of polymeric micelles as nanocarriers for bio-orthogonal catalysts

Bio-orthogonal chemistry is a powerful tool to selectively conduct non-natural reactions in biological environments with a high degree of precision, especially the transformation of biologically inert prodrugs to active compounds. Many transition metals are excellent candidates as catalysts for such reactions, but generally lack the specificity in prodrug activation at the required biological site.

By encapsulating metal catalysts in micellar nanocarriers, the EPR effect can be exploited to accumulate catalytic micelles at a tumour site and subsequently utilize them for activating prodrugs and enhancing the therapeutic effect. The hydrophobic core of the micelles provides a more efficient environment for the catalytic activity of the transition metals than otherwise available in biological conditions.¹ Additionally, the polymeric shell can protect the catalysts and provides a platform for further functionalization.

Our main goal is to understand the structure-property relationship of the catalytic micelles by varying the hydrophobic end-groups, metals and the coordinating ligands. Thus, we have prepared micelles assembled from PEG-dendron hybrids, which are covalently linked to the catalytic sites. The PEGs forming the hydrophilic segment of the micelles, will stabilize the micelle in the biological environment and increase the retention time in the blood stream without generating an immune response. The hydrophobic segment will be based on dendritic structures due to their high structural precision and modularity, which allow tuning of the amphiphilicity of the polymers and their micellar stability.

This micellar catalytic system has the potential to enhance the therapeutic effect by improving the specificity of bio-orthogonal catalysts and essentially bring us a step closer to make enzyme-like catalysis possible.

(1) Liu, Y.; Pujals, S.; Stals, P. J. M.; Paulöhrl, T.; Presolski, S.I.; Meijer, E.W.; Albertazzi, L.; Palmans, A.R.A. Catalytically Active Single-Chain Polymeric Nanoparticles: Exploring Their Functions in Complex Biological Media. J. Am. Chem. Soc. 2018, 140 (9), 3423–3433.