Vertex Engineering of the Dodecaborate-Based Broadband Membrane Carriers

The cytosolic delivery of hydrophilic cargo across live cell membranes can be challenging and common undesirable effects include membrane damage, cell death, and endosomal entrapment of cargo. Densely halogenated boron clusters have been recently shown to possess promising membrane transport properties for a variety of cargo molecules; however, increased activity has also been correlated with notable toxicity, particularly in the case of iodinated variants. In this work, we report that replacing several of the halogen moieties with hydroxyl groups significantly reduces the cytotoxicity of the resulting perfunctionalized dodecaborate-based derivatives. Live cell imaging studies using a model peptide tagged with a fluorophore demonstrate that the transport potential of this new class of cluster-based carriers can be maintained even with vertex differentiation. Additional experiments using a lipophilic probe suggest that cluster-cargo interactions in solution can lead to altered delivery outcomes for certain dyes used in live-cell staining. Altogether, we demonstrate a method to modulate the toxicity and effectiveness of a boron cluster-based, intracellular delivery platform using hydroxylation and show that the use of these halogenated compounds may result in intricate interactions with specific cargo molecules.