Platinum-Based Two-Photon Photosensitizer Responsive to NIR Light in Tumor Hypoxia Microenvironment

Platinum-based
photosensitizers are promising anticancer agents
in photodynamic therapy. The cytotoxic effects primarily arise from
the production of singlet oxygen and platination of DNA. However,
their efficacy is limited by drug resistance and hypoxic tumor microenvironment.
A naphthalimide-modified cyclometalated platinum­(II) complex PtPAN
[PA = N-(2-(diethylamino)­ethyl)­picolinamide, N = N-(2′-ethylhexyl)-4-ethynyl-1,8-naphthalimide] is
designed to conquer these problems. PtPAN generates ROS efficiently
under both normoxia and hypoxia. It does not interact with DNA and
shows low cytotoxicity in the dark, while it kills tumor cells via
ROS under near-infrared light irradiation; moreover, it inhibits tumor
growth in mice at a low light dose with negligible side effects. PtPAN
is the first reported platinum-based photosensitizer that is unreactive
to DNA in the dark but highly cytotoxic upon near-infrared (NIR) irradiation
for oxygen-independent photodynamic therapy. Owing to its two-photon
excitation property (λ = 825 nm), PtPAN may be suitable for
the treatment of deep solid tumors.