Tuning Exciton Coupling of Non-Conjugated Cyanine Dimers for Efficient Photodynamic Immunotherapy

Cyanine dyes usually serve as good fluorescence probes but not as efficient photosensitizers owing to the spin-forbidden intersystem crossing process and short excited-state lifetime. Nevertheless, the structure-derived energy release from the excited state could enable dyes to function efficiently. In this work, we developed cyanine dimers ( 2 o -Cy, 2 m -Cy, and 2 p -Cy ) based on exciton coupling effects by connecting two Cy5.5 molecules at the N -indole site with nonconjugated ortho / meta / para -bis(bromomethyl)benzene linkers. These dimers exhibited significantly enhanced molar extinction coefficients (32–45 × 10 4 M cm –1 ) as well as satisfactory triplet excited-state quantum yields (32–44%) and lifetimes (10.6–11.9 μs), leading to a substantially enhanced reactive oxygen species production along with efficient antitumor activity under both normoxic and hypoxic conditions. Furthermore, 2 p -Cy NPs ablated primary tumors, inhibited distant tumor growth, and prevented metastatic regrowth via photoinduced innate immune activation. This dimer-based strategy represents a powerful approach to develop high-performance photosensitive dyes for antitumor photodynamic immunotherapy.