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 <i>via</i> 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 <i>via</i> 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.