Dimerized Pentamethine Cyanines for Synergistically Boosting Photodynamic/Photothermal Therapy

ABSTRACT Photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged promising applications in both fundamental research and clinical trials. However, it remains challenging to develop ideal photosensitizers (PSs) that concurrently integrate high photostability, large near‐infrared absorptivity, and efficient therapeutic capabilities. Herein, we reported a sample engineering strategy to afford a benzene‐fused Cy5 dimer ( Cy‐D‐5 ) for synergistically boosting PDT/PTT applications. Intriguingly, Cy‐D‐5 exhibits a tendency to form both J ‐aggregates and H ‐aggregates in phosphate‐buffered saline, which show a long‐wavelength absorption band bathochromically shifted to 810 nm and a short‐wavelength absorption band hypsochromically shifted to 745 nm, respectively, when compared to its behavior in ethanol (778 nm). Density‐functional theory calculations combined with time‐resolved transient optical spectroscopy analysis reveal that the fused dimer Cy‐D‐5 exhibits a low Δ E ST (0.51 eV) and efficient non‐radiative transition rates (12.6 times greater than that of the clinically approved PS‐indocyanine green [PS‐ ICG ]). Furthermore, the Cy‐D‐5 demonstrates a higher photosensitizing ability to produce 1 O 2 , stronger photothermal conversion efficiency ( η = 64.4%), and higher photostability compared with ICG . These combined properties enable Cy‐D‐5 to achieve complete tumor ablation upon 808 nm laser irradiation, highlighting its potential as a powerful and dual‐function phototherapeutic agent. This work may offer a practical strategy for engineering other existing dyes to a red‐shifted spectral range for various phototherapy applications.