Enhancing Intersystem Crossing by Intermolecular Dimer-Stacking of Cyanine as Photosensitizer for Cancer Therapy

Development of new photosensitizers(PSs)with high singlet oxygen quantumyield and minimal side effects is of great interest in photodynamic therapy(PDT).Herein,a facile strategy to significantly improve photosensitization has been demonstrated for the first time with two pentamethine dyes connected by a varying alkyl chain resulting in a series of cyanine dimers.The photophysical properties of the dimerswere studied with steady-state optical spectroscopies,a timecorrelated single photon counting technique,and laser flash photolysis spectrometry.X-ray crystallography confirmed that the molecular packing modes of Cy-Bu-D and Cy-He-D were dominated by H-aggregation.The H-aggregation by dimerization suppresses the radiative singlet decay,which helps to stabilize the highly efficient triplet excitation state.Moreover,the dimers show more intensewavelength absorption in the nearinfrared(ɛ1.5-2.0 times more than monomer Cy-H at 650 nm),better singlet oxygen quantum yield,and a longer triplet-state lifetime than monomer Cy-H,providing excellent performance as a triplet PS.In vivo experiments demonstrated that Cy-He-D successfully suppresses tumor growth after PDT treatment.This work is beneficial to the design of novel heavy atom free PSs for PDT-based theranostic systems.