Photosensitizer-pendant biotinylated polyester as a nanocarrier for targeted photodynamic therapy

Combinatorial cancer therapy that combines photodynamic therapy with chemotherapy has gained tremendous importance in recent times. Reactive oxygen species (ROS) generation in cancer cells via photosensitizer-loaded polymeric nanoparticles represents one of the non-invasive methods for cancer treatment. As a proof of concept, herein, we demonstrate a molecular design based on a fully degradable polyester scaffold featuring a photosensitizer for targeted ROS generation in cancer cells. An enzymatically degradable, amphiphilic polyester was synthesized by organocatalyzed step-growth polymerization via a transesterification reaction between an activated diester and functional diols, incorporating a phenothiazine dye as the photosensitizer and biotin as the targeting ligand, since biotin receptors are known to be overexpressed in cancer cells. The polymer self-assembled into nanoaggregates in water, exhibiting selective uptake in cancer cells (HeLa and MCF7) with ROS-generating ability upon light irradiation, which caused significant cytotoxic effects. In addition, the hydrophobic core within the nanoaggregates exhibits the ability to encapsulate a chemotherapeutic drug, doxorubicin, and selectively release it in cancer cells.