(502f) Biodegradable Small Polymersomes with Encapsulated Indocyanine Green J-Aggregates for Photoacoustic Cancer Imaging

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J-aggregates (ICGJ), one of the only FDA-approved exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to 40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80-90nm will enhance the ability to penetrate tumors, while conjugation with EGFR targeting cetuximab antibodies results in high specificity in breast cancer cells. Even when exposed to serum, the 14 nm thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 hours with a high level of near-infrared (NIR) absorbance (I₈₉₀/I₇₈₅ ratio of approximately 5.0) to generate strong PA signals. The PA signal of polymersome-labeled cancer cells increased 3.5-5-fold at 895 nm excitation as a function of the level of EGFR expression on the breast cancer cells, indicating excellent selectivity. The cells were successfully detected in tissue mimicking phantoms with PAI in proportion to their quantity up to a depth of 5 mm, given the high ICGJ loading using a linear array transducer. This demonstrates excellent sensitivity that is clinically relevant to applications such as a tumor margin detection, evaluation of lymph nodes for presence of micrometastasis, and laparoscopic imaging procedures. In the future, in vivo evaluation of ICGJ-Ps will be conducted to illustrate the utility of these polymersomes for tumor detection and therapy monitoring.