Macromolecular Cobalt Carbonyl Complexes Encapsulated in a Click-Cross-Linked Micelle Structure as a Nanoparticle To Deliver Cobalt Pharmaceuticals

Abstract

Block copolymers poly(trimethylsilyl propargyl methacrylate)-block-poly(poly(ethylene glycol) methyl ether methacrylate) (P(TMS-PAMA)-b-P(PEGMA)) were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequent removal of the trimethylsilyl protective groups on the P(TMS-PAMA)(24)-b-P(PEGMA)(40) polymer with tetra-n-butylammonium fluoride hydrate lead to the polymer P(PAMA)(24)-b-P(PEGMA)(40) with pendant alkyne groups, which self-assembled in aqueous solution into micelles with hydrodynamic diameters of less than 20 nm. The alkyne groups in the core took on two functions, acting as a ligand for Co(2)(CO)(8) to generate a derivative of the antitumor agents based on (alkyne)Co(2)(CO)(6) as well as an anchor point for the cross-linking of micelles via click chemistry. The click process was shown to be highly efficient with the two types of cross-linker employed: 1,2-bis-(2-azidoethoxy)ethane and bis-(azidoethyl)disulfide, with almost all of the cross-linker reacting with the micelle at room temperature. The cross-linking density was influenced by the amount of added cross-linker leaving a well-defined amount of alkyne groups that were utilized in the formation of the cobalt complexes. The successful complexation was confirmed via UV/vis and FT-IR spectroscopy. With the formation of (alkyne)Co(2)(CO)(6) moieties in the core, the un-cross-linked and cross-linked micelles were found to almost double in size. The resulting Co-loaded un-cross-linked micelles were observed to be highly toxic to L929 fibroblast cells, while the cross-linking of the micelle was shown to reduce the toxicity.