Nanostructure‐Driven Indocyanine Green Dimerization Generates Ultra‐Stable Phototheranostics Nanoparticles

Abstract

AbstractIndocyanine green (ICG) is the only near‐infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano‐dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J‐aggregation of ICG‐dimer, resulting in a narrow, red‐shifted (780 nm→894 nm) and intense (≈2‐fold) absorbance. Compared to ICG, Nano‐dICG demonstrated superior photothermal conversion (2‐fold higher), significantly reduced photodegradation (−9.6 % vs. −46.3 %), and undiminished photothermal effect (7 vs. 2 cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano‐dICG enabled real‐time tracking of its delivery to mouse tumors within 24 h by photoacoustic imaging at NIR wavelength (890 nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure‐driven ICG dimerization leads to an ultra‐stable phototheranostic platform.