Rational design of a dual organelle-targeted photosensitizer with dual-color emission for photodynamic therapy and cell death self-reporting

Photosensitizers with organelle targeting play a vital role in image-guided photodynamic therapy (PDT). However, photosensitizers with the ability for dual-organelle targeting and dual-color emission are still lacking. Rational design of such photosensitizers with dual-organelle targeting and dual-color emission characteristics is of great significance for efficient enhancement of the performance of theranostics, but remains a challenge. Here we show a rational design to construct a dual organelle-targeted photosensitizer with dual-color emission by introducing cyano groups. To this end, two new photosensitizers TPA-2Py+ and TPA-2PyA+ with the electron donor (D: triphenylamine, TPA)-π bridge (π: benzene ring)-electron acceptor (A: vinyl/cyanovinyl pyridinium, Py/PyA) (D-π-A) structure were synthesized. Both of them exhibit effective singlet oxygen generation due to the strong D-π-A strength. TPA-2Py+ could light up the mitochondria of HeLa cells with near-infrared (NIR) emission. However, TPA-2PyA+ molecule possesses two additional cyano groups compared with TPA-2Py+, and enabled simultaneous locating into the lysosome and nucleolus with NIR and green fluorescence, respectively. Meanwhile, TPA-2PyA+ not only exhibited the ability to kill the cancer cells under light irradiation, but also to self-report the cell death in PDT via observing the change of emission color. This study offers an effective way for developing multifunctional photosensitizers for cancer theranostics.