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

• Published in: Biomacromolecules 2009-12, Vol.10 (12), p.3215-3226
• Main Authors: Withey, Alexander B. J, Chen, Gaojian, Nguyen, T. L. Uyen, Stenzel, Martina H
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Applied sciences; Biological and medical sciences; Cell Line, Tumor; Cobalt - administration & dosage; Cobalt - chemistry; Drug Carriers; Exact sciences and technology; Fibroblasts - drug effects; General pharmacology; Medical sciences; Mice; Micelles; Nanoparticles - chemistry; Organic polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polymers with particular properties; Polymethacrylic Acids - chemistry; Preparation, kinetics, thermodynamics, mechanism and catalysts
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm901050x

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 Co2(CO)8 to generate a derivative of the antitumor agents based on (alkyne)Co2(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)Co2(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.