Affiliation: | 1. Princess Margaret Cancer Centre, University Health Network, 101 College Street, PMCRT 5-354, Toronto, ON, M5G1L7 Canada;2. Sao Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Brazil;3. Sao Carlos Institute of Chemistry, University of Sao Paulo, Sao Carlos, Brazil;4. Princess Margaret Cancer Centre, University Health Network, 101 College Street, PMCRT 5-354, Toronto, ON, M5G1L7 Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada;5. Institute of Physics, Pontificia Universidad Católica de Chile, 7820436 Santiago, Chile |
Abstract: | Indocyanine 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. |