An Activatable Heavy-Atom-Free Upconversion Photosensitizer for Targeted Imaging and Treatment of Tumors

Photodynamic
therapy (PDT) is an innovative and promising
method
for treating tumors that has attracted significant interest but still
faces several challenges, such as a lack of selectivity, deep penetration
of light, and efficient ROS generation. To address these challenges,
we optimized and synthesized a series of photosensitizers and successfully
developed a heavy-atom-free near-infrared FUCL photosensitizer NFh-NMe-2.
This photosensitizer can generate singlet oxygen (1O2) and induce cellular apoptosis under 808 nm light. For the
safe ablation of microtumors in vivo, an activatable FUCL photosensitizer
NFh-NTR was developed based on the overexpression of nitroreductase
(NTR). NFh-NTR could be activated by NTR, leading to the release of
the photosensitizer NFh-NMe-2, restoring the fluorescence signal,
and effectively killing tumor cells under 808 nm light irradiation.
This work opens new possibilities in the chemical design of an FUCL
photosensitizer for cancer treatment.