It is well known that cationic polymers can disrupt cell membranes, most famously for disrupting bacterial membranes which are 'more anionic' than mammalian. However, these polymers can be used to kill cancerous cells, but avoiding non-specific toxicity to healthy cells and blood cells is a major problem. Most work in this field involves making minor changes through co-polymerization in the hope of making the polymers more specific. In this work, we instead engineered the cancer cells to 'capture' the polymer. We used metabolic oligosaccharide engineering to install azide groups selectivity on cancer cells, or cancer spheroids, and using alkyne polymers we could 'guide them' to the cells. This lead to increased toxicity and hence a wider therapeutic window. We showed this with several cell line and spheroids and also showed the covalent targetting induced additional mechanisms of cell death.

Read the paper here in Chemical Science

Covalent Cell Surface Recruitment of Chemotherapeutic Polymers Enhances Selectivity and Activity