Photoacoustic imaging of stimuli-responsive red blood cell drug delivery agents

Long circulation lifetime, large therapeutic payload, and inherent biocompatibility make engineered red blood cells (RBC) an attractive therapeutic delivery agent. However, drug release from conventional RBC carriers is diffusion limited and cannot be spatiotemporally controlled, thereby precluding targeted delivery to specific tissues. We have developed modified RBC carriers intended to function as image-guided therapeutic delivery agents. These new RBC carriers contain acoustically activatable perfluorocarbon droplets to enable ultrasound-mediated drug release, are loaded with iron oxide nanoparticles to permit magnetic targeting, and contain indocyanine green (ICG) dye to allow photoacoustic (PA) tracking of RBC accumulation. In this work, we evaluate the feasibility of detecting ICG-loaded RBCs against a whole blood background via spectroscopic PA imaging. We also characterize the increase in PA signal resultant from magnetic targeting of ICG-loaded RBCs.