Stimuli-Responsive Nanoparticles Based on Interaction of Metallacarborane with Poly(ethylene oxide)

Abstract

We report the first evidence that the antiviral active (inhibitor of HIV protease) boron cluster [3-cobalt bis(1,2-dicarbollide)]− anion, CoD−, interacts and forms a stable complex with one of the most widely used polymeric components of drug delivery systems: poly(ethylene oxide), PEO. The metallacarborane/polymer complex is insoluble in aqueous solutions. The amount of the precipitate depends on concentration of alkaline or earth-alkaline cations. The formation of insoluble complex is the result of a combination of several factors. One of the decisive contributions is the formation of dihydrogen bonds between negatively charged hydrogen atoms attached to boron atoms and slightly positively charged H atoms in repeating −CH2−CH2−O− units. It is also important that alkaline cations interact with oxygen atoms of PEO. The formation of the insoluble NaCoD/PEO complex can be exploited in design of water-soluble [3-cobalt bis(1,2-dicarbollide)]-containing nanoparticles which could offer applications in medicine. We studied the boron cluster interaction with a well-defined double hydrophilic block copolymer: poly(ethylene oxide)-block-poly(methacrylic acid), PEO−PMA. The interaction leads to a spontaneous formation of core−shell nanoparticles. The insoluble core contains the PEO/CoD− complex, while the polyanionic PMA blocks, which do not interact with the cobaltacarborane, form the pH-responsive micellar shell and stabilize the particles in aqueous media. The nanoparticles were studied by light and X-ray scattering, NMR spectroscopy, electrophoresis, and microscopy techniques like AFM and cryo-TEM. It was found that the cores are not completely frozen in aqueous media. Their composition depends on salt concentration, and the metallacarborane can diffuse from/into the nanoparticle after the salinity change.