Nano-Armoring of Enzymes: Rational Design of Polymer-Wrapped Enzymes

Methods Enzymol. 2017:590:381-411. doi: 10.1016/bs.mie.2017.01.007. Epub 2017 Mar 9.

Abstract

The formulation in which therapeutic proteins are administered plays a key role in retaining their biological activity. Enzyme wrapping, using synthetic polymers, is a strategy employed to provide enzymes with lower immunogenicity, longer circulation times, and better targeting capabilities. Protein-polymer complexation methods, involving covalent, noncovalent, and electrostatic interactions, that can provide means to develop formulations for retaining enzyme stability are discussed in this chapter. Amphiphilic self-cross-linkable polymer was used to encapsulate capsase-3 enzyme in the nanogel, while inverse emulsion polymerization method was used to entrap α-glucosidase enzyme in the nanogel. These nanogels were characterized by dynamic light scattering, transmission electron microscopy, and gel electrophoresis. Upon release of caspase-3 enzyme from polymeric nanogel, it retained nearly 86% of its original activity. Similarly, α-glucosidase that was encased in the acid cleavable polymeric nanogel exhibited substantial activity after release under acidic conditions (pH 5, 48h). Nano-armoring of the enzymes were nearly complete and provided high yields of the encased enzyme.

Keywords: Capsase; Electrostatic complexation; Emulsion polymerization; Lysosomes; Nanogels; Polymer wrapping; Protein encapsulation; Protein–polymer conjugates; Responsive; β-Galactosidase.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Caspase 3 / chemistry*
  • Emulsions
  • Enzyme Assays
  • Enzyme Stability
  • Enzymes, Immobilized / chemistry*
  • Nanostructures / chemistry*
  • Polymerization
  • Proteolysis

Substances

  • Emulsions
  • Enzymes, Immobilized
  • Caspase 3