Enzyme Induced Formation of Monodisperse Hydrogel Nanoparticles Tunable in Size

Abstract

We report a novel approach to synthesize monodisperse hydrogel nanoparticles that are tunable in size. The distinctive feature of our approach is the use of a multicopper oxidase enzyme, laccase, as both a biocatalyst and template for nanoparticle growth. We utilize the ferroxidase activity of laccase to initiate localized production of iron(III) cations from the oxidation of iron(II) cations. We demonstrate that nanoparticles are formed in a dilute polymer solution of alginate as a result of cross-linking between alginate and enzymatically produced iron(III) cations. Exerting control over the enzymatic reaction allows for nanometer-scale tuning of the hydrogel nanoparticle radii in the range of 30− 100 nm. The nanoparticles and their growth kinetics were characterized via dynamic light scattering, atomic force microscopy, and UV−vis spectroscopy. This finding opens up a new avenue for the synthesis of tunable nanoscale hydrogel particles for biomedical applications.

Iron(iii)-cross-linked alginate hydrogels: a critical review

“…Enzymatic reactions can be used to produce Fe 3+ -Alg monodisperse nanoparticles. 80 Multi-copper oxidase enzyme laccase greatly accelerates the oxidation of Fe 2+ to Fe 3+ by dissolved oxygen. If the reaction is conducted in the presence of sodium alginate the reluctant Fe 3+ cations are instantly trapped by alginate chains near the enzyme molecule producing a Fe 3+cross-linked shell around it growing with nearly constant rates for every enzyme molecule.…”

“…Enzymatic reactions can be used to produce Fe 3+ -Alg monodisperse nanoparticles. 80 The electrodeposition conditions were optimized for a graphite electrode at 35 mM Fe 2+ , 1.5% (w/v) NaAlg and 0.8 V (vs. Ag|AgCl) for 60 seconds. 47 It should be noted that the required applied potential might be different for electrodes made of different materials or with chemically modified surfaces.…”

Oxidoreductase‐Initiated Radical Polymerizations to Design Hydrogels and Micro/Nanogels: Mechanism, Molding, and Applications

“…Here, the chelation effects between polysaccharides and metal ions have been utilized for the preparation of enzymatically cross‐linked nanogels ( Figure a). Bocharova et al prepared a monodisperse, alginate‐based nanogel with tunable size using laccase as both a template and catalyst . First, biocompatible alginate was electrostatically adsorbed around a laccase core.…”

“…a) Enzyme‐mediated radical cross‐linked micro/nanogels were created based on the chelation effects between polysaccharides and metal ions and laccase‐induced oxidation of iron(II) to iron(III), and b) laccase‐mediated radical cross‐linked polysaccharide GCS. a) Reproduced with permission . Copyright 2015, American Chemical Society.…”

Peroxidase-Mediated In Situ Fabrication of Multi-Stimuli-Responsive and Dynamic Protein Nanogels from Tyrosine-Conjugated Biodynamer and Ovablumin

“…Horseradish peroxidase (HRP) has been utilized to prepare hydrogels via HRP-mediated oxidative coupling of phenol and aniline derivatives with the aid of hydrogen peroxide (H 2 O 2 ). − However, few studies on enzymatically cross-linked nanogels were reported. Bocharova et al utilized laccase as both a biocatalyst and template and fabricated alginate nanogels . Haag and co-workers fabricated cross-linked dendritic polyglycerol (dPG) nanogels by HRP-catalyzed oxidative cross-linking of phenolic derivatized dendrimer in an inverse miniemulsion, and the dPG nanogels provided efficient scaffolds for active protein encapsulation .…”