Liposomal J-Aggregates of Indocyanine Green as a Multifunctional Contrast Agent for Photoacoustic Imaging and Photothermal Therapy

One of the major barriers to further clinical adoption of photoacoustic imaging (PAI) and photothermal therapy (PTT) is a lack of versatile and multi-faceted contrast agents. While indocyanine green (IcG) has gained considerable attention as a promising contrast agent, it is severely limited by rapid clearance time, low photostability, and a peak absorbance wavelength that coincides with hemoglobin. Herein, Liposomal J-aggregates of Indocyanine green (LJA) are presented as a superior alternative to generic IcG. They are a facilely produced, biodegradable nanoparticle offering advantageous physiochemical properties. J-aggregation results in a redshifted peak absorbance of increased magnitude and higher photostability compared to IcG. Liposome encapsulation increases circulation time leading to improved tumor uptake. Monte Carlo modeling of light interaction with tissue suggests that these improved optical properties make LJA a better contrast agent for PTT not only at longer wavelengths like 852nm and 890nm, but also at the commonly available and widely used 808nm. <i>In vitro</i> and <i>in vivo</i> testing support first approximations from modelling as LJA provide significantly higher photoacoustic signal, show increased tumor uptake, reach significantly higher temperatures under photothermal irradiation, and have the capacity to reduce tumor growth following therapy.