In recent years, photodynamic therapy
(PDT) has drawn much attention
as a noninvasive and safe cancer therapy method due to its fine controllability,
good selectivity, low systemic toxicity, and minimal drug resistance
in contrast to the conventional methods (for example, chemotherapy,
radiotherapy, and surgery). However, some drawbacks still remain for
the current organic photosensitizers such as low singlet oxygen (1O2) quantum yield, poor photostability, inability
of absorption in the near-infrared (NIR) region, short excitation
wavelength, and limited action radius of singlet oxygen, which will
strongly limit the PDT treatment efficiency. As a consequence, the
development of efficient photosensitizers with high singlet oxygen
quantum yield, strong fluorescent emission in the aggregated state,
excellent photostability, NIR excitation wavelength ranging in the
biological transparency window, and highly specific targeting to mitochondria
is still in great demand for the enhancement of PDT treatment efficiency.
In this study, two new two-photon AIEgens TPPM and TTPM based on a rigid D−π–A skeleton have
been designed and synthesized. Both AIEgens TPPM and TTPM show strong aggregation-induced emission (AIE) with the
emission enhancement up to 290-folds, large two-photon absorption
with the two-photon absorption cross section up to 477 MG, and highly
specific targeting to mitochondria in living cells with good biocompatibility.
They can serve as two-photon bioprobes for the cell and deep tissue
bioimaging with a penetration depth up to 150 μm. Furthermore,
high 1O2 generation efficiency with high 1O2 quantum yield under white light irradiation
has been found for both TPPM and TTPM and
high PDT efficiency to HeLa cells under white light irradiation has
also been proven. To the best of our knowledge, AIEgens in this work
constitute one of the strongest emission enhancements and one of the
highest 1O2 generation efficiencies in the reported
organic AIEgens so far. The great AIE feature, large two-photon absorption,
high specificity to mitochondria in living cells, and high PDT efficiency
to living cells as well as excellent photostability and biocompatibility
of these novel AIEgens TPPM and TTPM reveal
great potential in clinical applications of two-photon cell and tissue
bioimaging and image-guided and mitochondria-targeted photodynamic
cancer therapy.