Scientists at UCLA have re-purposed vault nanoparticles, ribonucleoprotein complexes that all mammalian cells have in the cytoplasm, to serve as drug ferries with large cargo holds. The advantages of using such nanoparticles is that they, by their nature, do not trigger an immune response, and they are small enough to travel to target sites and large enough to bring along substantial drug loads.
A vault is essentially barrel-shaped nanocapsule with a large, hollow interior — properties that make them ripe for engineering into a drug-delivery vehicles. The ability to encapsulate small-molecule therapeutic compounds into vaults is critical to their development for drug delivery.
Recombinant vaults are nonimmunogenic and have undergone significant engineering, including cell-surface receptor targeting and the encapsulation of a wide variety of proteins.
"By packaging drug-loaded NDs into the vault lumen, the ND and its contents would be shielded from the external medium," Buehler said. "Moreover, given the large vault interior, it is conceivable that multiple NDs could be packaged, which would considerably increase the localized drug concentration."
According to researcher Zhou, a professor of microbiology, immunology and molecular genetics and director of the CNSI’s Electron Imaging Center for NanoMachines, electron microscopy and X-ray crystallography studies have revealed that both endogenous and recombinant vaults have a thin protein shell enclosing a large internal volume of about 100,000 cubic nanometers, which could potentially hold hundreds to thousands of small-molecular-weight compounds.
The recombinant vaults are engineered to encapsulate the highly insoluble and toxic hydrophobic compound all-trans retinoic acid (ATRA) using a vault-binding lipoprotein complex that forms a lipid bilayer nanodisk.
Image: Single-particle electron microscope tomography reconstruction, which reveals that a fully assembled drug-loaded nanodisk (red) can be packaged into the vault lumen (green). The electron micrograph in the background shows negatively stained vaults containing nanodisks.
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