Effect of Injection Routes on the Biodistribution, Clearance, and Tumor Uptake of Carbon Dots

The emergence of photoluminescent carbon-based nanomaterials has shown exciting potential in the development of benign nanoprobes. However, the <i>in vivo</i> kinetic behaviors of these particles that are necessary for clinical translation are poorly understood to date. In this study, fluorescent carbon dots (C-dots) were synthesized and the effect of three injection routes on their fate <i>in vivo</i> was explored by using both near-infrared fluorescence and positron emission tomography imaging techniques. We found that C-dots are efficiently and rapidly excreted from the body after all three injection routes. The clearance rate of C-dots is ranked as intravenous > intramuscular > subcutaneous. The particles had relatively low retention in the reticuloendothelial system and showed high tumor-to-background contrast. Furthermore, different injection routes also resulted in different blood clearance patterns and tumor uptakes of C-dots. These results satisfy the need for clinical translation and should promote efforts to further investigate the possibility of using carbon-based nanoprobes in a clinical setting. More broadly, we provide a testing blueprint for <i>in vivo</i> behavior of nanoplatforms under various injection routes, an important step forward toward safety and efficacy analysis of nanoparticles