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

Cobalt bisdicarbollides (COSANs) are inorganic boron-basedanionsthat have been previously reported to permeate by themselves throughlipid bilayer membranes, a propensity that is related to their superchaotropiccharacter. We now introduce their use as selective and efficient molecularcarriers of otherwise impermeable hydrophilic oligopeptides throughboth artificial and cellular membranes, without causing membrane lysisor poration at low micromolar carrier concentrations. COSANs transportnot only arginine-rich but also lysine-rich peptides, whereas low-molecular-weightanalytes such as amino acids as well as neutral and anionic cargos(phalloidin and BSA) are not transported. In addition to the unsubstitutedisomers (known as ortho- and meta-COSAN), four derivatives bearing organic substituents or halogenatoms have been evaluated, and all six of them surpass establishedcarriers such as pyrenebutyrate in terms of activity. U-tube experimentsand black lipid membrane conductance measurements establish that thetransport across model membranes is mediated by a molecular carriermechanism. Transport experiments in living cells showed that a fluorescentpeptide cargo, FITC-Arg(8), is delivered into the cytosol.