Proteins conjugated to poly (butyl cyanoacrylate) nanoparticles as potential neuroprotective agents
Reukov, V.; Maximov, V.; Vertegel, A.
Biotechnology and Bioengineering 108(2): 243-252
ISSN/ISBN: 0006-3592 PMID: 20939007 DOI: 10.1002/bit.22958
Poly(butyl cyanoacrylate) (PBCA) nanoparticles (NPs) can penetrate blood-brain barrier providing the means for drug delivery to the central nervous system. Here, we study attachment of superoxide dismutase (SOD) and anti-glutamate N-methyl D-aspartate receptor 1 (NR1) antibody to PBCA NPs with the ultimate goal to design neuroprotective therapeutics for treatment of secondary spinal cord injury. Synthesis of monodispersed, ∼200 nm-diameter PBCA NPs was performed using polymerization at pH 2.0 with Dextran 70,000 as the stabilizer. Sulfo-HSAB spacers were used to covalently attach SOD and NR1 antibodies to the dextran-coated NPs. The prepared protein-NP conjugates possessed SOD activity and were capable of binding to rat cerebellar neurons. Thus, SOD and NR1 antibodies may be simultaneously attached to PBCA NPs while retaining at least a fraction of enzymatic activity and receptor-binding ability. The conjugates showed neuroprotective efficacy in vitro with rat cerebellar cell cultures challenged by superoxide.