Lectins on Polymer Scaffolds for Superselective Targeting of Cancer Cells
A major challenge in all cancer therapies is to selectively target tumour cells whilst leaving the healthy cells unaffected. Current treatment methods often produce significant side effects because they are unable to identify tumour cells with sufficient selectivity. The aim of this research project will be to develop a new generation of probes that are able to recognise specific cell types, such as cancer cells, with exquisite selectivity.
We have recently demonstrated that multivalent probes based on a flexible polymer scaffold can effectively discriminate surfaces based on the density of surface receptors (Dubacheva et al, PNAS, 2015, 112:5579). This ability is now termed ‘superselective targeting’ as it is superior to the conventional targeting methods which can discriminate cells by receptor type but not by the density of a given receptor. Superselective targeting is of particular interest for cancer cells where carbohydrate epitopes (glycan antigens) also present on normal cells are expressed at higher densities.
In this project the ESR will develop ‘superselective’ probes based on lectins (glycan-binding proteins) and polymer scaffolds and use these to demonstrate the superselective recognition of cancer cells. They will combine advanced protein biochemistry and bioconjugation techniques to engineer lectins and multivalent probes that recognise specifically the tumour-associated glycan antigens overexpressed on cancer cells.
The ESR will also design model cell surfaces that present the glycan antigens at defined densities, and use biophysical and cell biology techniques to evaluate superselective recognition of model cell surfaces and live cells. This project thus requires multiple disciplines to work hand in hand, and the synBiocarb network will provide the ideal training environment.
University of Leeds
Supervisor Dr Ralf Richter