Vasculature organotropism in drug delivery

[Display omitted] Over the past decades, there has been an exponential increase in the development of preclinical and clinical nanodelivery systems, and recently, an accelerating demand to deliver RNA and protein-based therapeutics. Organ-specific vasculature provides a promising intermediary for site-specific delivery of nanoparticles and extracellular vesicles to interstitial cells. Endothelial cells express organ-specific surface marker repertoires that can be used for targeted delivery. This article highlights organ-specific vasculature properties, nanodelivery strategies that exploit vasculature organotropism, and overlooked challenges and opportunities in targeting and simultaneously overcoming the endothelial barrier. Impediments in the clinical translation of vasculature organotropism in drug delivery are also discussed.