New Cy5 photosensitizers for cancer phototherapy: a low singlet-triplet gap provides high quantum yield of singlet oxygen

Abstract

Highly efficient triplet photosensitizers (PSs) have attracted increasing attention in cancer photodynamic therapy where photo-induced reactive oxygen species (ROSs, such as singlet oxygen) are producedviasinglet-triplet intersystem crossing (ISC) of the excited photosensitizer to kill cancer cells. However, most PSs exhibit the fatal defect of a generally less-than-1% efficiency of ISC and low yield of ROSs, and this defect strongly impedes their clinical application. In the current work, a new strategy to enhance the ISC and high phototherapy efficiency has been developed, based on the molecular design of a thio-pentamethine cyanine dye (TCy5) as a photosensitizer. The introduction of an electron-withdrawing group at themeso-position of TCy5 could dramatically reduce the singlet-triplet energy gap (ΔEst) value (from 0.63 eV to as low as 0.14 eV), speed up the ISC process (τISC= 1.7 ps), prolong the lifetime of the triplet state (τT= 319 μs) and improve singlet oxygen (1O2) quantum yield to as high as 99%, a value much higher than those of most reported triplet PSs. Furtherin vitroandin vivoexperiments have shown that TCy5-CHO, with its efficient1O2generation and good biocompatibility, causes an intense tumor ablation in mice. This provides a new strategy for designing ideal PSs for cancer photo-therapy.