Tuning Exciton Coupling of Non-Conjugated Cyanine Dimers for Efficient Photodynamic Immunotherapy
Hua Gu, Puan Yuan, Juan Zhang, Xiang Xia, Qingze Pan, Wenkai Liu, Xueze Zhao, Wen Sun, Jianjun Du, Jiangli Fan, Xiaojun Peng
Abstract
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.