DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Enzyme Induced Formation of Monodisperse Hydrogel Nanoparticles Tunable in Size

Abstract

Here, 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. Moreover, the nanoparticles and their growth kinetics were characterized via dynamic light scattering, atomic force microscopy, and UV–vis spectroscopy. Our finding opens up a new avenue for the synthesis of tunable nanoscale hydrogel particles for biomedical applications.

Authors:
 [1];  [2];  [2];  [1];  [3];  [2];  [2];  [1];  [1];  [4];  [5]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
  3. Univ. of Pennsylvania, Philadelphia, PA (United States)
  4. Clarkson Univ., Potsdam, NY (United States)
  5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Sciences (CNMS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1185968
Grant/Contract Number:  
AC05-00OR22725; DMR-1408811
Resource Type:
Accepted Manuscript
Journal Name:
Chemistry of Materials
Additional Journal Information:
Journal Volume: 27; Journal Issue: 7; Journal ID: ISSN 0897-4756
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE

Citation Formats

Bocharova, Vera, Sharp, Danna, Jones, Aaron, Cheng, Shiwang, Griffin, Philip J., Agapov, Alexander L., Voylov, Dmitry, Wang, Yangyang, Kisliuk, Alexander, Melman, Artem, and Sokolov, Alexei P. Enzyme Induced Formation of Monodisperse Hydrogel Nanoparticles Tunable in Size. United States: N. p., 2015. Web. doi:10.1021/acs.chemmater.5b00187.
Bocharova, Vera, Sharp, Danna, Jones, Aaron, Cheng, Shiwang, Griffin, Philip J., Agapov, Alexander L., Voylov, Dmitry, Wang, Yangyang, Kisliuk, Alexander, Melman, Artem, & Sokolov, Alexei P. Enzyme Induced Formation of Monodisperse Hydrogel Nanoparticles Tunable in Size. United States. https://doi.org/10.1021/acs.chemmater.5b00187
Bocharova, Vera, Sharp, Danna, Jones, Aaron, Cheng, Shiwang, Griffin, Philip J., Agapov, Alexander L., Voylov, Dmitry, Wang, Yangyang, Kisliuk, Alexander, Melman, Artem, and Sokolov, Alexei P. Mon . "Enzyme Induced Formation of Monodisperse Hydrogel Nanoparticles Tunable in Size". United States. https://doi.org/10.1021/acs.chemmater.5b00187. https://www.osti.gov/servlets/purl/1185968.
@article{osti_1185968,
title = {Enzyme Induced Formation of Monodisperse Hydrogel Nanoparticles Tunable in Size},
author = {Bocharova, Vera and Sharp, Danna and Jones, Aaron and Cheng, Shiwang and Griffin, Philip J. and Agapov, Alexander L. and Voylov, Dmitry and Wang, Yangyang and Kisliuk, Alexander and Melman, Artem and Sokolov, Alexei P.},
abstractNote = {Here, 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. Moreover, the nanoparticles and their growth kinetics were characterized via dynamic light scattering, atomic force microscopy, and UV–vis spectroscopy. Our finding opens up a new avenue for the synthesis of tunable nanoscale hydrogel particles for biomedical applications.},
doi = {10.1021/acs.chemmater.5b00187},
journal = {Chemistry of Materials},
number = 7,
volume = 27,
place = {United States},
year = {Mon Mar 09 00:00:00 EDT 2015},
month = {Mon Mar 09 00:00:00 EDT 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

A Solvent-Free Thermosponge Nanoparticle Platform for Efficient Delivery of Labile Proteins
journal, October 2014

  • Choi, Won Il; Kamaly, Nazila; Riol-Blanco, Lorena
  • Nano Letters, Vol. 14, Issue 11
  • DOI: 10.1021/nl502994y

Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates
journal, February 2014

  • Dong, Y.; Love, K. T.; Dorkin, J. R.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 11
  • DOI: 10.1073/pnas.1322937111

Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery
journal, May 2008

  • Liong, Monty; Lu, Jie; Kovochich, Michael
  • ACS Nano, Vol. 2, Issue 5
  • DOI: 10.1021/nn800072t

Gold Nanoparticles: A Revival in Precious Metal Administration to Patients
journal, October 2011

  • Thakor, A. S.; Jokerst, J.; Zavaleta, C.
  • Nano Letters, Vol. 11, Issue 10
  • DOI: 10.1021/nl202559p

Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery
journal, January 2013


Nanoparticle therapeutics: an emerging treatment modality for cancer
journal, September 2008

  • Davis, Mark E.; Chen, Zhuo; Shin, Dong M.
  • Nature Reviews Drug Discovery, Vol. 7, Issue 9
  • DOI: 10.1038/nrd2614

Assessing Nanoparticle Toxicity
journal, July 2012


Strategies in the design of nanoparticles for therapeutic applications
journal, July 2010

  • Petros, Robby A.; DeSimone, Joseph M.
  • Nature Reviews Drug Discovery, Vol. 9, Issue 8
  • DOI: 10.1038/nrd2591

Biocompatibility of engineered nanoparticles for drug delivery
journal, March 2013


The development of microgels/nanogels for drug delivery applications
journal, April 2008


Nanogels as Pharmaceutical Carriers: Finite Networks of Infinite Capabilities
journal, July 2009

  • Kabanov, Alexander V.; Vinogradov, Serguei V.
  • Angewandte Chemie International Edition, Vol. 48, Issue 30
  • DOI: 10.1002/anie.200900441

Self-assembled Nanogel Engineering for Advanced Biomedical Technology
journal, March 2012

  • Sasaki, Yoshihiro; Akiyoshi, Kazunari
  • Chemistry Letters, Vol. 41, Issue 3
  • DOI: 10.1246/cl.2012.202

Self-aggregates of hydrophobized polysaccharides in water. Formation and characteristics of nanoparticles
journal, June 1993

  • Akiyoshi, Kazunari; Deguchi, Shigeru; Moriguchi, Nobuhiro
  • Macromolecules, Vol. 26, Issue 12
  • DOI: 10.1021/ma00064a011

Microscopic Structure and Thermoresponsiveness of a Hydrogel Nanoparticle by Self-Assembly of a Hydrophobized Polysaccharide
journal, February 1997

  • Akiyoshi, Kazunari; Deguchi, Shigeru; Tajima, Hitoshi
  • Macromolecules, Vol. 30, Issue 4
  • DOI: 10.1021/ma960786e

Structural Determination and Interior Polarity of Self-Aggregates Prepared from Deoxycholic Acid-Modified Chitosan in Water
journal, January 1998

  • Lee, Kuen Yong; Jo, Won Ho; Kwon, Ick Chan
  • Macromolecules, Vol. 31, Issue 2
  • DOI: 10.1021/ma9711304

Aggregation in Water of Dextran Hydrophobically Modified with Bile Acids
journal, October 1999

  • Nichifor, Marieta; Lopes, António; Carpov, Adrian
  • Macromolecules, Vol. 32, Issue 21
  • DOI: 10.1021/ma990408k

Self-Assembled Nanogel of Hydrophobized Dendritic Dextrin for Protein Delivery
journal, July 2009

  • Ozawa, Yayoi; Sawada, Shin-ichi; Morimoto, Nobuyuki
  • Macromolecular Bioscience, Vol. 9, Issue 7
  • DOI: 10.1002/mabi.200800288

Self-Cross-Linked Polymer Nanogels: A Versatile Nanoscopic Drug Delivery Platform
journal, December 2010

  • Ryu, Ja-Hyoung; Chacko, Reuben T.; Jiwpanich, Siriporn
  • Journal of the American Chemical Society, Vol. 132, Issue 48
  • DOI: 10.1021/ja1069932

Surfactant-Free Synthesis of Biodegradable, Biocompatible, and Stimuli-Responsive Cationic Nanogel Particles
journal, September 2013

  • Urakami, Hiromitsu; Hentschel, Jens; Seetho, Kellie
  • Biomacromolecules, Vol. 14, Issue 10
  • DOI: 10.1021/bm401039r

Release dynamics of ciprofloxacin from swellable nanocarriers of poly(2-hydroxyethyl methacrylate): an in vitro study
journal, June 2010

  • Chouhan, Raje; Bajpai, Anil K.
  • Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 6, Issue 3
  • DOI: 10.1016/j.nano.2009.11.006

pH sensitive swelling and releasing behavior of nano-gels based on polyaspartamide graft copolymers
journal, April 2011

  • Kim, Sunmi; Kim, Ji-Heung; Kim, Dukjoon
  • Journal of Colloid and Interface Science, Vol. 356, Issue 1
  • DOI: 10.1016/j.jcis.2011.01.003

Lidocaine loaded biodegradable nanospheres
journal, August 1999


Enzyme-mediated fast in situ formation of hydrogels from dextran–tyramine conjugates
journal, January 2007


Tailorable Cell Culture Platforms from Enzymatically Cross-Linked Multifunctional Poly(ethylene glycol)-Based Hydrogels
journal, January 2013

  • Menzies, Donna J.; Cameron, Andrew; Munro, Trent
  • Biomacromolecules, Vol. 14, Issue 2
  • DOI: 10.1021/bm301652q

Enzymatically Crosslinked Dextran-Tyramine Hydrogels as Injectable Scaffolds for Cartilage Tissue Engineering
journal, August 2010

  • Jin, Rong; Moreira Teixeira, Liliana S.; Dijkstra, Pieter J.
  • Tissue Engineering Part A, Vol. 16, Issue 8
  • DOI: 10.1089/ten.tea.2009.0764

In Situ Forming Hydrogels Based on Tyramine Conjugated 4-Arm-PPO-PEO via Enzymatic Oxidative Reaction
journal, February 2010

  • Park, Kyung Min; Shin, Young Min; Joung, Yoon Ki
  • Biomacromolecules, Vol. 11, Issue 3
  • DOI: 10.1021/bm9012875

Multicopper oxidase-1 is a ferroxidase essential for iron homeostasis in Drosophila melanogaster
journal, July 2012

  • Lang, M.; Braun, C. L.; Kanost, M. R.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 33
  • DOI: 10.1073/pnas.1208703109

Multi-Copper Oxidases and Human Iron Metabolism
journal, June 2013

  • Vashchenko, Ganna; MacGillivray, Ross
  • Nutrients, Vol. 5, Issue 7
  • DOI: 10.3390/nu5072289

Electrochemically Controlled Drug-Mimicking Protein Release from Iron-Alginate Thin-Films Associated with an Electrode
journal, January 2012

  • Jin, Zhiyuan; Güven, Güray; Bocharova, Vera
  • ACS Applied Materials & Interfaces, Vol. 4, Issue 1
  • DOI: 10.1021/am201578m

Electrochemically stimulated release of lysozyme from an alginate matrix cross-linked with iron cations
journal, January 2012

  • Jin, Zhiyuan; Harvey, Anthony M.; Mailloux, Shay
  • Journal of Materials Chemistry, Vol. 22, Issue 37
  • DOI: 10.1039/c2jm32008h

Photodegradable Iron(III) Cross-Linked Alginate Gels
journal, July 2012

  • Narayanan, Remya P.; Melman, Galina; Letourneau, Nicolas J.
  • Biomacromolecules, Vol. 13, Issue 8
  • DOI: 10.1021/bm300707a

Dioxygen Reactivity of Laccase: Dependence on Laccase Source, pH, and Anion Inhibition
journal, January 2001


Preparation of Ionically Cross-Linked Pectin Nanoparticles in the Presence of Chlorides of Divalent and Monovalent Cations
journal, September 2013

  • Jonassen, Helene; Treves, Alessandro; Kjøniksen, Anna-Lena
  • Biomacromolecules, Vol. 14, Issue 10
  • DOI: 10.1021/bm4008474

Enzyme Kinetics
book, January 2008


Enzymatically Cross-Linked Hyperbranched Polyglycerol Hydrogels as Scaffolds for Living Cells
journal, October 2014

  • Wu, Changzhu; Strehmel, Christine; Achazi, Katharina
  • Biomacromolecules, Vol. 15, Issue 11
  • DOI: 10.1021/bm500705x

Crystal Structure of a Laccase from the Fungus Trametes versicolor at 1.90-Å Resolution Containing a Full Complement of Coppers
journal, August 2002

  • Piontek, Klaus; Antorini, Matteo; Choinowski, Thomas
  • Journal of Biological Chemistry, Vol. 277, Issue 40
  • DOI: 10.1074/jbc.M204571200

Isolation and structural analysis of the laccase gene from the ligninegrading fungus Phlebia radiata
journal, July 1991

  • Saloheimo, M.; Niku-Paavola, M. -L.; Knowles, J. K. C.
  • Journal of General Microbiology, Vol. 137, Issue 7
  • DOI: 10.1099/00221287-137-7-1537

Characterization and structural analysis of the laccase I gene from the newly isolated ligninolytic basidiomycete PM1 (CECT 2971)
journal, December 1993


Effect of Ca 2+ , Ba 2+ , and Sr 2+ on Alginate Microbeads
journal, April 2006

  • Mørch, Ýrr A.; Donati, Ivan; Strand, Berit L.
  • Biomacromolecules, Vol. 7, Issue 5
  • DOI: 10.1021/bm060010d

Reexamining the Egg-Box Model in Calcium−Alginate Gels with X-ray Diffraction
journal, February 2007

  • Li, Liangbin; Fang, Yapeng; Vreeker, Rob
  • Biomacromolecules, Vol. 8, Issue 2
  • DOI: 10.1021/bm060550a

Works referencing / citing this record:

Oxidoreductase-Initiated Radical Polymerizations to Design Hydrogels and Micro/Nanogels: Mechanism, Molding, and Applications
journal, March 2018

  • Wang, Xia; Chen, Shuangshuang; Wu, Dongbei
  • Advanced Materials, Vol. 30, Issue 17
  • DOI: 10.1002/adma.201705668