Atropine-functionalized gold nanoparticles binding to muscarinic receptors after passage across the intestinal epithelium

Abstract

Gold nanoparticles have a high potential to be a treatment of diseases by their specific drug delivery properties and multivalent receptor stimulation. For the present project, spherical gold nanoparticles were synthesized and functionalized with the muscarinic receptor antagonist atropine (Au-MUDA-AT NPs). The diameter of the gold core could precisely be controlled by using different synthetic methods and reducing agents resulting in functionalized gold nanoparticles with diameters ranging from 8 to 16 nm. The ability to interact with intestinal muscarinic receptors is size-dependent. When using intestinal chloride secretion induced by the stable acetylcholine derivative, carbachol, as read-out, the strongest inhibition, i.e. the most efficient blockade of muscarinic receptors, was observed with 13 nm sized Au-MUDA-AT NPs. Functional experiments indicate that Au-MUDA-AT NPs with a diameter of 14 nm are able to pass the intestinal mucosa in a time-dependent manner after administration to the intestinal lumen. For example, luminally administered Au-MUDA-AT NPs inhibited contractions of the small intestinal longitudinal muscle layer induced by electrical stimulation of myenteric neurons. A similar inhibition of basolateral epithelial receptors was observed after luminal administration of Au-MUDA-AT NPs when using carbachol-induced chloride secretion across the intestinal epithelium as a test system. Thus, Au-MUDA-AT NPs might be a therapeutic tool for the modulation of intestinal secretion and motility after oral application in the future.

High-Yield 99mTc Labeling of Gold Nanoparticles Carrying Atropine and Adrenaline

“…We prepared mixed-ligand shell Au NPs carrying both a chelator and a bioactive ligand. Here, we have chosen MUDA-AT (atropine) and MUDA-ADR (adrenaline), respectively, whose syntheses have been described previously. ,− Mixed-ligand shell Au NPs represent pharmacologically relevant samples for potential application in theragnostics.…”

“…23 Therefore, atropine functionalized Au NPs are attractive for overcoming these spasms. 22 However, the biodistribution of these NPs in the body remains poorly understood.…”

“…Its most prominent chemistry, however, is represented by gold nanoparticle (Au NP) dispersions, which are particularly recognizable for their size-dependent plasmon resonance and the resulting intense red, wine-red, or even violet colors. Applications of Au NPs range from catalysis , to medicine, and functional molecules and frameworks have been attached to NPs, e.g., proteins − or deoxyribonucleic acid (DNA) scaffolds, , to targeting ligands, such as drugs − and antibodies, − as well as biogenic compounds. − …”

“…Its receptor antagonist atropine or other anticholinergic drugs are currently being studied to treat intestinal spasms . Therefore, atropine functionalized Au NPs are attractive for overcoming these spasms . However, the biodistribution of these NPs in the body remains poorly understood.…”