Kwon N, Jasinevicius GO, Kassab G, Ding L, Bu J, Martinelli LP, Ferreira VG, Dhaliwal A, Chan HHL, Mo Y, Bagnato VS, Kurachi C, Chen J, Zheng G

Angewandte Chemie

DOI: 10.1002/anie.202305564

Indocyanine green (ICG) is the only 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 nanoemulsion, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J-aggregation of ICG-dimer, resulting in a narrow, red-shifted (780nm → 894nm) 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 tumor within 24h by photoacoustic imaging at a NIR wavelength (890nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure-driven ICG dimerization leads to ultra-stable phototheranostic platform.