A lipid droplet-targeted AIE photosensitizer for efficient multi-type ROS generation and breast cancer photodynamic therapy.

Photodynamic therapy (PDT) is a promising non-invasive strategy for breast cancer, yet its clinical translation is hindered by fluorescence quenching, insufficient reactive oxygen species (ROS) generation and poor tumor targeting. Herein, a novel lipid droplet-targeted aggregation-induced emission (AIE) photosensitizer CTC was designed and synthesized. CTC has a large Stokes shift of 150 nm to avoid self-absorption and exhibits typical AIE properties in aqueous environments. Under white light irradiation, it efficiently generates three cytotoxic ROS (1O2, ·OH, O2•-), with a high colocalization coefficient of 0.95 with lipid droplets in 4 T1 cells. CTC shows excellent biocompatibility in the dark and potent phototoxicity under illumination. In vivo, CTC combined with light significantly inhibits 4 T1 tumor growth without systemic toxicity. Density functional theory calculations elucidate its multi-type ROS generation mechanism, providing a novel candidate and new insight for safe and efficient breast cancer PDT.