DNA-AgNC Loaded Liposomes for Measuring Cerebral Blood Flow Using Two-Photon Fluorescence Correlation Spectroscopy

Unraveling the transport of drugs and nanocarriers in cerebrovascular networks is important for pharmacokinetic and hemodynamic studies but is challenging due to the complexity of sensing individual particles within the circulatory system of a live animal. Here, we demonstrate that a DNA-stabilized silver nanocluster (DNA-Ag16NC) that emits in the first near-infrared window upon two-photon excitation in the second NIR window can be used for multiphoton in vivo fluorescence correlation spectroscopy for the measurement of cerebral blood flow rates in live mice with high spatial and temporal resolution. To ensure bright and stable emission during in vivo experiments, we loaded DNA-Ag16NCs into liposomes, which served the dual purposes of concentrating the fluorescent label and protecting it from degradation. DNA-Ag16NC-loaded liposomes enabled the quantification of cerebral blood flow velocities within individual vessels of a living mouse.