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 and photothermal therapy. When compared to monomeric IcG, L-JA are characterized by longer circulation, improved photostability, elevated absorption at longer wavelengths, and increased photoacoustic signal generation. However, the documented methods for production of L-JA vary widely. We developed an approach to efficiently form IcG J-aggregates (IcG-JA) directly in liposomes at elevated temperatures. Aggregating within fully formed liposomes ensures particle uniformity and allows for control of J-aggregate size. L-JA have unique properties compared to IcG. L-JA provide significant contrast enhancement in photoacoustic images for up to 24 hours after injection, while IcG and unencapsulated IcG-JA are cleared within an hour. L-JA allow for more accurate photoacoustic-based sO2 estimation and particle tracking compared to IcG. Furthermore, photothermal heating of L-JA with an 852nm laser is demonstrated to be more effective at lower laser powers than conventional 808nm 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.