Therapeutic applications of responsive organic photocatalytic polymers, enabling in situ drug activation

Abstract

Targeted prodrug activation within the acidic tumour microenvironment is needed to limit off-target effects in chemotherapy. This in combination with photodynamic generation of reactive oxygen species (ROS) can be used for efficient remediation of cancerous tissue. To achieve this, pH-responsive polymers with photocatalytic units that become activated in the acidic pH of the tumour microenvironment have been created. Four model prodrug linkages in small molecule substrates have been investigated along with a model polymer-based prodrug. We have demonstrated the pH-dependent activation of model prodrug molecules, due to conformational changes of the pH-responsive photocatalytic polymers. Additionally, a prodrug of the common skin cancer chemotherapy drug 5-fluorouracil (5FU) could be photocatalytically activated and could induce cell death in cancer cells.