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)-pi bridge (pi: benzene ring)-electron acceptor (A: vinyl/cyanovinyl pyridinium, Py/PyA) (D-pi-A) structure were synthesized. Both of them exhibit effective singlet oxygen generation due to the strong D-pi-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.

Automated summary

We successfully designed a photosensitizer with dual-organelle targeting and dual-color emission by introducing cyano groups. This photosensitizer can light up the mitochondria, locate into the lysosome and nucleolus, and self-report cell death by observing the change of emission color.