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 produced via singlet-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 the meso-position of TCy5 could dramatically reduce the singlet-triplet energy gap (ΔE _st) value (from 0.63 eV to as low as 0.14 eV), speed up the ISC process (τ _ISC = 1.7 ps), prolong the lifetime of the triplet state (τ _T = 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. Further in vitro and in vivo experiments have shown that TCy5-CHO, with its efficient ¹O₂ generation and good biocompatibility, causes an intense tumor ablation in mice. This provides a new strategy for designing ideal PSs for cancer photo-therapy.

SUBMITTER: Ma H 

PROVIDER: S-EPMC8549779 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature