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Unlike passive diffusion, which is largely restricted to small lipophilic compounds, RMT exploits endogenous receptors expressed on brain endothelial cells, allowing the transport of biologics and engineered nanoparticles that would otherwise be excluded from the CNS ( Principally, RMT involves ligand binding to receptors on the luminal endothelial surface, followed by receptor-mediated endocytosis, intracellular trafficking, and exocytosis into the brain parenchyma