Encapsulation and stabilization of indocyanine green within poly(styrene-alt-maleic anhydride) block-poly(styrene) micelles for near-infrared imaging

Indocyanine green ICG is a Federal Drug Administration- approved near-infrared imaging agent susceptible to chemical degra- dation, nonspecific binding to blood proteins, and rapid clearance from the body. In this study, we describe the encapsulation of ICG within polymeric micelles formed from polystyrene-alt-maleic anhydride-block-polystyrenePSMA-b-PSTY diblock copolymers to stabilize ICG for applications in near-infrared diagnostic imaging. In aqueous solution, the diblock copolymers self-assemble to form highly stable micelles approximately 55 nm in diameter with a critical micelle concentration CMC of 1m g/L. Hydrophobic ICG salts readily partition into the PSTY core of these micelles with high effi- ciency, and produce no change in micelle morphology or CMC. Once loaded in the micelle core, ICG is protected from aqueous and ther- mal degradation, with no significant decrease in fluorescence emis- sion over 14 days at room temperature and retaining 63% of its origi- nal emission at 37°C. Free ICG does not release rapidly from the micelle core, with only 11% release over 24 h. The ICG-loaded mi- celles do not exhibit significant cell toxicity. This system has the po- tential to greatly improve near-infrared imaging in breast cancer de- tection by increasing the stability of ICG for formulation/admin- istration, and by providing a means to target ICG to tumor tissue.