Erythrocyte-Derived Theranostic Nanoplatforms for Near Infrared Fluorescence Imaging and Photodestruction of Tumors.

Nanoparticles activated by near infrared (NIR) excitation provide a capability for optical imaging and photo-destruction of tumors. We have engineered optical nano-constructs derived from erythrocytes, which are doped with the FDA-approved NIR dye, indocyanine green (ICG). We refer to these constructs as NIR erythrocyte-mimicking transducers (NETs). Herein, we investigate the photo-theranostic capabilities of NETs for fluorescence imaging and photo-destruction of SKBR3 breast cancer cells, and subcutaneous xenograft tumors in mice. Our cellular studies demonstrate that NETs are internalized by these cancer cells, and localized to their lysosomes. As evidenced by NIR fluorescence imaging and in vivo laser irradiation studies, NETs remain available within tumors at 24 hours post intravenous injection. In response to continuous wave 808 nm laser irradiation at intensity of 680 mW/cm2 for 10-15 minutes, NETs mediate the destruction of cancer cells and tumors in mice through synergistic photochemical and photothermal effects. We demonstrate that NETs are effective in mediating photo-activation of Caspase-3 to induce tumor apoptosis. Our results provide support in effectiveness of NETs as theranostic agents for fluorescence imaging and photo-destruction of tumors, and their role in photo-induced apoptosis initiated by their localization to lysosomes.