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Nanostructure-Driven Indocyanine Green Dimerization Generates Ultra-Stable Phototheranostics Nanoparticles
Authors:Dr. Nahyun Kwon  Gabriel O. Jasinevicius  Dr. Giulia Kassab  Lili Ding  Jiachuan Bu  Letícia P. Martinelli  Dr. Vinicius G. Ferreira  Alexander Dhaliwal  Dr. Harley H. L. Chan  Yulin Mo  Dr. Vanderlei S. Bagnato  Prof. Dr. Cristina Kurachi  Dr. Juan Chen  Prof. Dr. Gang Zheng  Prof. Dr. Hilde H. Buzzá
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.
Keywords:Indocyanine Green  Nanoemulsion  Photoacoustic Imaging  Photostability  Photothermal Therapy
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