Multivalent stimulation of β<sub>1</sub>-, but not β<sub>2</sub>-receptors by adrenaline functionalised gold nanoparticles

Mattern, Annabelle; Claßen, Rebecca; Wolf, Annemarie; Pouokam, Ervice; Schlüter, Klaus‐Dieter; Wickleder, Ma­thias S.; Diener, Martin

doi:10.1039/d2na00171c

Cited by 2 publications

(8 citation statements)

References 57 publications

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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. − …”

Section: Introductionmentioning

confidence: 99%

“…Scheme 3. NP Functionalization in a Ligand Exchange Reaction According to Mattern et al21 and Subsequent Radiolabelling of Au-MUAM-PADA NPs with [ 99m Tc(OH 2 ) 3 (CO) 3 ] +a…”

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

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This work focuses on the synthesis, purification, and analytical characterization of novel multifunctional Au NPs radiolabeled with 99mTc. These mixed-ligand shell Au NPs represent pharmacologically relevant samples for potential application in theragnostics. A ligand using a plain linker with a rather long chain consisting of 10 CH2 groups and a thiol moiety along with the PADA chelator has been used for both the attachment to the Au NP surface and for the 99mTc(CO)3 + complexation. We have combined this with our approach of stabilizing Au NP without any PEG or other stabilizing groups. Thus, monoligand shell Au NPs were radiolabeled by different strategies (prelabeling and postlabeling). Additionally, pharmacologically relevant Au NPs were synthesized carrying both a biofunctionalization with either atropine or adrenaline and the 99mTc radiolabel. All samples were obtained in very good yields (up to 80% of the total activity loaded onto the column) and completely/particularly purified using desalting columns. Detailed analytical characterization of the Au NPs before and after radiolabeling has proven the NPs’ robustness throughout the process. Their intact functionalization, shape, and stability was confirmed by transmission electron microscopy (TEM), ultraviolet/visible (UV/vis) spectroscopy, dynamic light scattering (DLS), and infrared (IR) spectroscopy. The presented strategy represents a versatile building block system that can be adapted to a variety of bioactive molecules and may be of high relevance for theragnostic applications.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

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

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“…9: 220244 4.4. General synthetic procedure for mercaptoundecanoic acid (MUDA) coordinated gold nanoparticles in H 2 O (according to the Stucky method modified by Mattern et al [8])…”

Section: Synthesis Of Au-citrate (ø 16 Nm) In H 2 Omentioning

confidence: 99%

“…Whereas our previous studies were designed to attach neurotransmitters or hormones stimulating distinct G-protein coupled receptors [8], the present experiments focus on the attachment of the receptor antagonist atropine. When absorbed after oral administration, atropine competes with acetylcholine and acts as blocker of muscarinic receptors including M 1 and M 3 receptors present at the basolateral membrane of the epithelium involved in the activation of epithelial secretion [27] or M 2 and M 3 receptors involved in the stimulation of gastrointestinal motility [28].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Multivalent stimulation of β₁-, but not β₂-receptors by adrenaline functionalised gold nanoparticles

Abstract: In this study, we present a strategy for the synthesis of catecholamine functionalised gold nanoparticles and investigated their multivalent interactions with adrenergic receptors in different biological systems. The catecholamines adrenaline...

Cited by 2 publications

References 57 publications

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

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

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

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Multivalent stimulation of β1-, but not β2-receptors by adrenaline functionalised gold nanoparticles

Abstract: In this study, we present a strategy for the synthesis of catecholamine functionalised gold nanoparticles and investigated their multivalent interactions with adrenergic receptors in different biological systems. The catecholamines adrenaline...

Cited by 2 publications

References 57 publications

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

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

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

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Multivalent stimulation of β₁-, but not β₂-receptors by adrenaline functionalised gold nanoparticles

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

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