Ex Vivo and In Vivo Evaluation of Dodecaborate-Based Clusters Encapsulated in Ferumoxytol Nanoparticles

Abstract

Host-guest interactions represent a growing research area with recent work demonstrating an ability to chemically manipulate both host molecules as well as guest molecules to vary the type and strength of bonding. Much less is known about the interactions of guest molecules and hybrid materials containing similar chemical features to typical macrocyclic hosts. This work uses in vitro and in vivo kinetic analyses to investigate the interaction of closo-dodecahydrododecaborate derivatives with ferumoxytol, an iron oxide nanoparticle with a carboxylated dextran coating. We find that several boron cluster derivatives can become encapsulated into ferumoxytol and the lack of pH dependence in these interactions suggests that ion pairing, hydrophobic/hydrophilic, or hydrogen bonding are not the driving force for encapsulation in this system. Biodistribution experiments in BALB/c mice show that this system is nontoxic at the reported dosage and demonstrate that encapsulation of dodecaborate-based clusters in ferumoxytol can alter the biodistribution of guest molecules.

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport

“…The most chaotropic cluster (B 12 I 12 2− ) is less useful because it causes membrane damage, while the smallest cluster (B 10 H 10 2− ) is the least active one because of its lowest chaotropicity (Figure 2e). Mechanistically, a higher chaotropicity is related to a larger cluster size, lower charge density, and increased polarizability of the clusters, which accounts for the higher affinity to biological components, both peptides and membranes, on account of favorable dehydration effects and dispersion interactions in aqueous solution [5,6,13,27,39–41] . This work serves as a blueprint for the design and implementation of chaotropic clusters and their formulations with potential membrane transporting capabilities.…”

Metallacarborane Cluster Anions of the Cobalt Bisdicarbollide-Type as Chaotropic Carriers for Transmembrane and Intracellular Delivery of Cationic Peptides

“…6 Recently, a new cell-biological as well as medicinal-chemical application line has been documented for icosahedral dodecaborates B 12 X 12 2− (X = H, Cl, Br, and I; Figure 1a), because their superchaotropic ionic character 7−13 enables their use as broadband membrane carriers, that is, they enable cellular uptake of a wide range of otherwise impermeable hydrophilic molecules, including amino acids, neurotransmitters, peptides, and drugs. 14,15 This, combined with their chemical inertness, 13,16−18 high water solubility, 13,17,19 and high biocompatibility, 3,5,13,14,20,21 defines a new research area in chaotropic inorganic cluster chemistry. Accordingly, it is of interest to investigate how variations in the boron cluster structure and topology affect their chaotropic character and, thus, their potential membrane carrier activity.…”

“…Boron-containing compounds have application potential in pharmaceutical chemistry, − with boron neutron capture therapy being the most prominent example . Recently, a new cell-biological as well as medicinal-chemical application line has been documented for icosahedral dodecaborates B 12 X 12 2– (X = H, Cl, Br, and I; Figure a), because their superchaotropic ionic character − enables their use as broadband membrane carriers, that is, they enable cellular uptake of a wide range of otherwise impermeable hydrophilic molecules, including amino acids, neurotransmitters, peptides, and drugs. , This, combined with their chemical inertness, ,− high water solubility, ,, and high biocompatibility, ,,,,, defines a new research area in chaotropic inorganic cluster chemistry. Accordingly, it is of interest to investigate how variations in the boron cluster structure and topology affect their chaotropic character and, thus, their potential membrane carrier activity.…”

Boron Cage Triggered Micellization of a Neutral–Cationic Block Copolymer and Preparation of Boron-Containing Layer-by-Layer Microparticles

“…Cobalt bis­(dicarbollide) anion-loaded tetrazine-functionalized gold nanoparticles (GNPs), , mesoporous silica nanoparticles (MSPs), , boron nitride nanotubes (BNNTs), boron analogues of carbon nanotubes, − and magnetic nanoparticles , have been explored for boron delivery. Recently, iron oxide nanoparticles with carboxylated dextran coatings, so-called “ferumoxytol”, have been explored for the encapsulation of several closo -dodecahydrododecaborate derivatives . Apart from inorganic nanomaterials, liposomes − and dendrimers were found to be promising carriers with respect to the amount of boron delivered to the tumor tissues.…”