A Facile Approach to Producing Liposomal J‐Aggregates of Indocyanine Green with Diagnostic and Therapeutic Potential

Abstract Liposomal J‐Aggregates of Indocyanine Green (L‐JA) can serve as a biocompatible and biodegradable nanoparticle for photoacoustic imaging (PAI) and photothermal therapy (PTT). When compared to monomeric indocyanine green (IcG), L‐JA is characterized by longer circulation, improved photostability, elevated absorption at longer wavelengths, and increased photoacoustic signal generation. However, the documented methods for the production of L‐JA vary widely. An approach to efficiently form IcG J‐aggregates (IcG‐JA) directly in liposomes at elevated temperatures is developed. Aggregating within fully formed liposomes ensures particle uniformity and allows for control of J‐aggregate size. L‐JA has unique properties compared to IcG. L‐JA provides significant contrast enhancement in photoacoustic images for up to 24 h after injection, while IcG and unencapsulated IcG‐JA are cleared within an hour. L‐JA allows for more accurate photoacoustic‐based blood oxygen saturation (sO 2 ) estimation and particle tracking compared to IcG. Furthermore, photothermal heating of L‐JA with an 852 nm laser is demonstrated to be more effective at lower laser powers than conventional 808 nm lasers for the first time. The presented technique offers an avenue for formulating a multi‐faceted contrast agent for photoacoustic imaging and photothermal therapy that offers significant advantages over other conventional agents.