Flow-guided carriers: an in vivo study in zebrafish embryos

Nanoparticle geometry plays a critical role in vascular transport, yet its influence in vivo remains incompletely understood. Here, we investigate the effect of particle shape on transport through the cardiovascular system of zebrafish embryos. Fluorescently labelled spherical and cylindrical polymer nanoparticles were injected into the circulation, and their spatiotemporal distribution was quantified by measuring fluorescence intensity within blood vessels at 2, 5, and 10 minutes post-injection, a temporal window that captures early hydrodynamic transport before cellular uptake mechanisms become dominant. Spherical nanoparticles exhibited a significantly faster increase in fluorescence intensity in small-diameter vessels compared with cylindrical counterparts, indicating enhanced access to the microvasculature. Critically, this study resolves intravascular distribution dynamics in the first 15 minutes of circulation, a temporal regime and anatomical compartment distinct from the organ-level biodistribution measured at 24 hours or later in conventional pharmacokinetic studies, providing data directly applicable to computational modeling of nanocarrier transport in vascular networks. These findings demonstrate a shape-dependent transport advantage for spherical nanoparticles in confined vascular networks and provide in vivo evidence to inform the rational design of nanoparticle-based delivery systems.