On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles
2021; National Academy of Sciences; Volume: 118; Issue: 52 Linguagem: Inglês
10.1073/pnas.2109256118
ISSN1091-6490
AutoresSean A. Dilliard, Qiang Cheng, Daniel J. Siegwart,
Tópico(s)Lipid Membrane Structure and Behavior
ResumoSignificance Liver accumulation represents a significant barrier in the development of therapeutically efficacious nanoparticle drug delivery systems. Using a series of lipid nanoparticles with distinct organ-targeting properties, we provide evidence for a plausible mechanism of action for nanoparticle delivery to non-liver tissues. Following intravenous injection, specific proteins in the blood are recruited to the nanoparticle’s surface based on its molecular composition and they endow it with a unique biological identity that governs its ultimate fate in the body. An innovative paradigm emerges from this mechanistic understanding of nanoparticle delivery—endogenous targeting—wherein the molecular composition of a nanoparticle is rationally engineered to interact with specific proteins in the blood to overcome liver accumulation and to target specific organs.
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