Yao Chen

• This thesis focuses on the delivery applications of cobalt bis(dicarbollide) (COSANs). Inspired by the characters of COSANs which are inorganic boron-based anions and have been previously reported to permeate by themselves through lipid bilayer membranes, a propensity that is related to their superchaotropic character, we decided to study their transport ability toward different cargos, including organic oligopeptides and proteins as well as inorganic ions. Firstly, we introduced COSANs as selective and highly efficient molecular carriers of impermeable hydrophilic oligopeptides through both artificial and cellular membranes, without causing membrane damage at micromolar carrier concentration. Importantly, cobalt bisdicarbollides transport not only arginine but also lysine peptides, while low-molecular weight analytes such as amino acids and neurotransmitters as well as neutral and anionic cargos (phalloidin and BSA) are not transported. By a combination of U-tube experiments and electrophysiology, we establish the transport is mediated by a carrier mechanism. Cellular experiments validate FITCArg8 delivery into the cytosol and nucleus by a combination of direct permeation and endocytosis. Secondly, the ability of COSAN 2 to selectively transport different types of protein cargos into both artificial vesicles and cells has been demonstrated. Especially, isoelectric points of proteins, that is electronic interaction between COSANs and proteins, presumably were the key factor of their delivery process mediated by COSAN. In relation to the CF assay, we proved that positively charged and neutral proteins are well transported by COSAN 2 at micromolar concentration while negatively charged proteins are not transported. Finally, we extended the application of COSANs to inorganic ion transport. pH-sensitive HPTS assay in combination with mechanism studies demonstrated that COSAN 4 exhibited the most efficient transport of Na+ and K+ flux by H+/K+ antiport mechanism.