Cancer-cell-specific Self-Reporting Photosensitizer for Precise Identification and Ablation of Cancer Cells

Cancer-cell-specific fluorescent photosensitizers (PSs)
are highly
desired molecular tools for cancer ablation with minimal damage to
normal cells. However, such PSs that can achieve cancer specification
and ablation and a self-reporting manner concurrently are rarely reported
and still an extremely challenging task. Herein, we have proposed
a feasible strategy and conceived a series of fluorescent PSs based
on simple chemical structures for identifying and killing cancer cells
as well as monitoring the photodynamic therapy (PDT) process by visualizing
the change of subcellular localization. All of the constructed cationic
molecules could stain mitochondria in cancer cells, identify cancer
cells specifically, and monitor cancer cell viability. Among these,
IVP-Br has the strongest ability to produce ROS, which serves as a
potent PS for specific recognition and killing of cancer cells. IVP-Br
could translocate from mitochondria to the nucleolus during PDT, self-reporting
the entire therapeutic process. Mechanism study confirms that IVP-Br
with light irradiation causes cancer cell ablation via inducing cell
cycle arrest, cell apoptosis, and autophagy. The efficient ablation
of tumor through PDT induced by IVP-Br has been confirmed in the 3D
tumor spheroid chip. Particularly, IVP-Br could discriminate cancer
cells from white blood cells (WBCs), exhibiting great potential to
identify circulating tumor cells (CTCs).