Nanotechnologies for cancer: developing new polymer-drug conjugates for the treatment of a range of cancers

About the Project

Polymer anticancer-drug conjugates are drug delivery systems in which a low molecular weight anticancer agent is covalently conjugated to a water-soluble polymeric carrier. Their main advantages compared to the parent free drug are: (i) passive accumulation in the tumour tissue by means of the well-described enhanced permeability and retention (EPR) effect, (ii) decreased toxicity, (iii) increased solubility (anticancer drugs are usually poorly water-soluble), (iv) bypassing of certain mechanisms of drug resistance such as P-glycoprotein mediated resistance. Following accumulation in the tumour tissue, polymer-drug conjugates are internalised into tumour cells by endocytosis and trafficked to the lysosomal compartment. In the lysosomes, the linker is cleaved in response to environmental stimuli (usually low pH or peptidases such as cathepsin B) and the drug is released.

This programme aims to develop new polymer-drug conjugates for the treatment of a range of cancers. In particular, the incorporation of drug-polymer linkers that are sensitive to enzymes within a range of tumours will be probed to potentially prepare prodrugs for cancer. These polymeric prodrugs should be inactive until they reach the enzyme required for drug release, and since the enzymes will be specific to tumours, selective delivery should result. This approach will present an important advantage compared to traditional polymer anticancer drug conjugates. Whilst the selectivity of the latter relies only on the EPR effect, the proposed system will display a double targeting mechanism: the EPR effect followed by specific activation in the tumour tissue.

The project is highly interdisciplinary and involves a collaboration between Med Chem (Prof Osborn) and Pharmaceutics (Greco)

Funding Notes

Applicants should hold, or expect to shortly gain, a 2(i) or better degree in a related discipline