Intravital Vascular Phototheranostics and Real-Time Circulation Dynamics of Micro- and Nano-sized Erythrocyte-Derived Carriers

Erythrocyte-based carriers can serve as theranostic platforms for delivery of imaging and therapeutic payloads. Engineering these carriers at micro- or nano-scales makes them potentially useful for broad clinical applications ranging from vascular diseases to tumor theranostics. Longevity of these carriers in circulation is important in delivering a sufficient amount of their payloads to the target. We have investigated the circulation dynamics of micro (~4.95 μm diameter) and nano (~91 nm diameter) erythrocyte-derived carriers in real time using near-infrared fluorescence imaging, and evaluated the effectiveness of such carrier systems in mediating photothermolysis of cutaneous vasculature in mice. Fluorescence emission half-lives of micro- and nano-sized carriers in response to a single intravenous injection were ~49 and ~15 minutes, respectively. A single injection of micro-sized carriers resulted in threefold increase in signal to noise ratio that remained nearly persistent over one hour of imaging time. Our results also suggest that a second injection of the carriers seven days later can induce a transient inflammatory response, as manifested by the apparent leakage of the carriers into the perivascular tissue. The administration of the carriers into the mice vasculature reduced the threshold laser fluence to induce photothermolysis of blood vessels from >65 to 20 J/cm(2). We discuss the importance of membrane physicochemical and mechanical characteristics in engineering erythrocyte-derived carriers, and considerations for their clinical translation.