Lipid membrane-camouflaged biomimetic nanoparticle for MicroRNA based therapeutic delivery to intestinal epithelial...

We have made artificial extracellular vesicles like nanoparticles that contain biologically active Agomir (miRNA mimic)/Antagomir (miRNA inhibitor) adsorbed on magnetic ZnO particles bound by a lipid bilayer membrane from Caco-2 cells (human colorectal adenocarcinoma), which we examined for use as therapeutic nanoparticles or as delivery vehicles for therapeutic agents to the gut epithelia. Magnetic ZnO nanoparticles were synthesized using Manganese doping in both solid-state reaction (SSR) and alkaline aqueous solution methods. The SSR method exhibited ferromagnetic behavior, whereas the alkaline solution method yielded a nanorod-like morphology. Encapsulation was demonstrated using mercaptosuccinic acid. These biocompatible nanoparticles, owing to their nanorod-like morphology with larger surface area, were used to adsorb miR200c antagomir/agomir molecules as well as assemble lipid membrane fragments from Caco-2 cells. We performed various in vivo efficacy studies of Caco-2 NanoVesicles (CNVs) (Caco-2NanoVesicles) or detrimental CNV (therapeutic Caco-2 NanoVesicles (tCNVs)) loaded with miR200c Agomir that degrade occludin protein-coding mRNA as a proof of concept for clinical use of the Antagomir counterpart. There was no discernible toxicity, mortality, or systemic inflammatory or immunological responses in mice following administration of either CNVs or tCNVs. tCNV administration enhances intestinal permeability in mice. This supports their use as biological Nano-therapeutics to restore the gut barrier.