On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles
Abstract
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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- December 2021
- DOI:
- 10.1073/pnas.2109256118
- Bibcode:
- 2021PNAS..11809256D