Enzymatic Cellular Nanoparticles Deliver Payloads across Mucosal Barriers

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Mucosal barriers impede drug delivery via oral or inhaled routes.
• Mucus, composed of glycosylated mucin proteins, is a significant obstacle to therapeutic bioavailability.
• Effective drug delivery requires strategies to penetrate these natural defenses.

Purpose of the Study:

• To engineer nanoparticles capable of enhanced mucopenetration.
• To overcome the limitations of mucosal barriers for therapeutic and prophylactic delivery.
• To develop a virus-mimicking system for improved drug transport.

Main Methods:

• Developed virus-mimicking enzymatic cellular nanoparticles by coating mRNA-loaded lipid nanoparticle cores with neuraminidase-expressing mammalian cell membrane.
• Genetically engineered neuraminidase protein onto cell membranes, inspired by influenza A virus.
• Utilized enzymatic activity to cleave sialic acid residues in the mucus matrix.

Main Results:

• In vitro studies confirmed nanoparticles effectively traversed artificial mucus layers.
• Demonstrated significantly enhanced mRNA delivery to epithelial cells.
• In vivo murine model experiments showed improved lung mRNA expression after intratracheal administration.

Conclusions:

• Enzyme-coated cellular nanoparticles show promise for overcoming mucosal barriers.
• Viral biomimicry offers a novel strategy for enhancing drug delivery and bioavailability.
• This approach has potential applications in therapeutics and prophylactics requiring mucosal penetration.