Synthesis of Micro-nanoparticles Using Ultrasound-Responsive Biomolecules

  • Kenji OkitsuEmail author
  • Francesca Cavalieri
Part of the SpringerBriefs in Molecular Science book series (BRIEFSMOLECULAR)


The ultrasonic crosslinking of biomacromolecules and biomolecules can be exploited to fabricate micro-nanodevices. In particular, biologically relevant molecules and macromolecules are desirable building blocks for engineering biomaterials. Ultrasonic synthesis, modification, and assembly of biomolecules and biomacromolecules enable the tuning of size, composition, degradability, surface properties, and biofunctionality of micro-nanodevices. Recent achievements in engineering of micro-nanodevices using ultrasound-responsive biomolecules such as proteins, amino acids, and phenolic molecules will be discussed in this section. These recent findings highlight the potential use of high- and low-frequency ultrasound techniques to fabricate innovative platforms for biomedical applications.


Protein-shelled microbubbles Phenols oligomerization Tyrosine oligomerization Self-assembly of phenolics 


  1. 1.
    R.M. Fitch, C. Tsai, Polymer colloids: particle formation in nonmicellar systems. J. Polym. Sci., Part C: Polym. Lett. 8(10), 703–710 (1970)Google Scholar
  2. 2.
    G. Cooper, F. Grieser, S. Biggs, Butyl acrylate/vinyl acetate copolymer latex synthesis using ultrasound as an initiator. J. Colloid Interface Sci. 184(1), 52–63 (1996)CrossRefPubMedGoogle Scholar
  3. 3.
    P. Kruus, D. McDonald, T. Patraboy, Polymerization of styrene initiated by ultrasonic cavitation. J. Phys. Chem. 91(11), 3041–3047 (1987)CrossRefGoogle Scholar
  4. 4.
    S. Biggs, F. Grieser, Preparation of polystyrene latex with ultrasonic initiation. Macromolecules 28(14), 4877–4882 (1995)CrossRefGoogle Scholar
  5. 5.
    S.K. Ooi, S. Biggs, Ultrasonic initiation of polystyrene latex synthesis. Ultrason. Sonochem. 7(3), 125–133 (2000)CrossRefPubMedGoogle Scholar
  6. 6.
    J. Zhang, Y. Cao, Y. He, Ultrasonically irradiated emulsion polymerization of styrene in the presence of a polymeric surfactant. J. Appl. Polym. Sci. 94(2), 763–768 (2004)CrossRefGoogle Scholar
  7. 7.
    Y. He, Y. Cao, Y. Fan, Using anionic polymerizable surfactants in ultrasonically irradiated emulsion polymerization to prepare polymer nanoparticles. J. Appl. Polym. Sci. 107(3), 2022–2027 (2008)CrossRefGoogle Scholar
  8. 8.
    Y. He, Y. Cao, Y. Liu, Initiation mechanism of ultrasonically irradiated emulsion polymerization. J. Polym. Sci., Part B: Polym. Phys. 43(18), 2617–2624 (2005)CrossRefGoogle Scholar
  9. 9.
    M.A. Bradley et al., Miniemulsion copolymerization of methyl methacrylate and butyl acrylate by ultrasonic initiation. Macromolecules 38(15), 6346–6351 (2005)CrossRefGoogle Scholar
  10. 10.
    H. Xia, Q. Wang, G. Qiu, Polymer-encapsulated carbon nanotubes prepared through ultrasonically initiated in situ emulsion polymerization. Chem. Mater. 15(20), 3879–3886 (2003)CrossRefGoogle Scholar
  11. 11.
    M. Bradley, F. Grieser, Emulsion polymerization synthesis of cationic polymer latex in an ultrasonic field. J. Colloid Interface Sci. 251(1), 78–84 (2002)CrossRefPubMedGoogle Scholar
  12. 12.
    F. Cavalieri et al., One-pot ultrasonic synthesis of multifunctional microbubbles and microcapsules using synthetic thiolated macromolecules. Chem. Commun. 47(14), 4096–4098 (2011)CrossRefGoogle Scholar
  13. 13.
    F. Cavalieri et al., Ultrasonic synthesis of stable, functional lysozyme microbubbles. Langmuir 24(18), 10078–10083 (2008)CrossRefPubMedGoogle Scholar
  14. 14.
    F. Cavalieri et al., Influence of the Morphology of Lysozyme-Shelled Microparticles on the Cellular Association, Uptake, and Degradation in Human Breast Adenocarcinoma Cells. Part. Part. Syst. Charact. 30(8), 695–705 (2013)CrossRefGoogle Scholar
  15. 15.
    M. Zhou, F. Cavalieri, M. Ashokkumar, Tailoring the properties of ultrasonically synthesised microbubbles. Soft Matter 7(2), 623–630 (2011)CrossRefGoogle Scholar
  16. 16.
    T.D. Tran et al., Clinical applications of perfluorocarbon nanoparticles for molecular imaging and targeted therapeutics. Int. J. Nanomed. 2(4), 515 (2007)Google Scholar
  17. 17.
    Y. Mine, F. Ma, S. Lauriau, Antimicrobial peptides released by enzymatic hydrolysis of hen egg white lysozyme. J. Agric. Food Chem. 52(5), 1088–1094 (2004)CrossRefPubMedGoogle Scholar
  18. 18.
    D. Cosgrove, C. Harvey, Clinical uses of microbubbles in diagnosis and treatment. Med. Biol. Eng. Compu. 47(8), 813–826 (2009)CrossRefGoogle Scholar
  19. 19.
    K. Ferrara, R. Pollard, M. Borden, Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. Annu. Rev. Biomed. Eng. 9, 415–447 (2007)CrossRefPubMedGoogle Scholar
  20. 20.
    M. Postema, Medical bubbles. Med. Phys. 32(5), 1450 (2005)CrossRefGoogle Scholar
  21. 21.
    P. Morse, K. Ingard, Theoretical Acoustics (McGrawHill, New York, 1968), Google Scholar: pp. 252–255Google Scholar
  22. 22.
    S.H. Bloch et al., Optical observation of lipid-and polymer-shelled ultrasound microbubble contrast agents. Appl. Phys. Lett. 84(4), 631–633 (2004)CrossRefGoogle Scholar
  23. 23.
    N. de Jong et al., Absorption and scatter of encapsulated gas filled microspheres: theoretical considerations and some measurements. Ultrasonics 30(2), 95–103 (1992)CrossRefPubMedGoogle Scholar
  24. 24.
    N. de Jong, L. Hoff, Ultrasound scattering properties of Albunex microspheres. Ultrasonics 31(3), 175–181 (1993)CrossRefPubMedGoogle Scholar
  25. 25.
    W.-S. Chen et al., A comparison of the fragmentation thresholds and inertial cavitation doses of different ultrasound contrast agents. J. Acoust. Soc. Am. 113(1), 643–651 (2003)CrossRefPubMedGoogle Scholar
  26. 26.
    F. Cavalieri et al., Antimicrobial and biosensing ultrasound-responsive lysozyme-shelled microbubbles. ACS Appl. Mater. Interfaces 5(2), 464–471 (2013)CrossRefPubMedGoogle Scholar
  27. 27.
    S. Chapalamadugu, G.R. Chaudhry, Microbiological and biotechnological aspects of metabolism of carbamates and organophosphates. Crit. Rev. Biotechnol. 12(5–6), 357–389 (1992)CrossRefPubMedGoogle Scholar
  28. 28.
    M.S. Ayyagari et al., Controlled free-radical polymerization of phenol derivatives by enzyme-catalyzed reactions in organic solvents. Macromolecules 28(15), 5192–5197 (1995)CrossRefGoogle Scholar
  29. 29.
    A. Nozoe et al., Germanium recovery using polyphenol microspheres prepared by horseradish peroxidase reaction. J. Chem. Technol. Biotechnol. 86(11), 1374–1378 (2011)CrossRefGoogle Scholar
  30. 30.
    B. Eker et al., Enzymatic polymerization of phenols in room-temperature ionic liquids. J. Mol. Catal. B Enzym. 59(1), 177–184 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    S. Dubey, D. Singh, R. Misra, Enzymatic synthesis and various properties of poly (catechol). Enzyme Microb. Technol. 23(7), 432–437 (1998)CrossRefGoogle Scholar
  32. 32.
    F.F. Bruno et al., Novel enzymatic polyethylene oxide-polyphenol system for ionic conductivity. J. Macromol. Sci. Part A 39(10), 1061–1068 (2002)CrossRefGoogle Scholar
  33. 33.
    Y.-J. Kim, H. Uyama, S. Kobayashi, Regioselective synthesis of poly (phenylene) as a complex with poly (ethylene glycol) by template polymerization of phenol in water. Macromolecules 36(14), 5058–5060 (2003)CrossRefGoogle Scholar
  34. 34.
    Y.J. Kim, H. Uyama, S. Kobayashi, Peroxidase-catalyzed oxidative polymerization of phenol with a nonionic polymer surfactant template in water. Macromol. Biosci. 4(5), 497–502 (2004)CrossRefPubMedGoogle Scholar
  35. 35.
    T. Heck et al., Enzyme-catalyzed protein crosslinking. Appl. Microbiol. Biotechnol. 97(2), 461–475 (2013)CrossRefPubMedGoogle Scholar
  36. 36.
    Z. Chen et al., Biocompatible, functional spheres based on oxidative coupling assembly of green tea polyphenols. J. Am. Chem. Soc. 135(11), 4179–4182 (2013)CrossRefPubMedGoogle Scholar
  37. 37.
    J. Fei et al., One-pot ultrafast self-assembly of autofluorescent polyphenol-based core@ shell nanostructures and their selective antibacterial applications. ACS Nano 8(8), 8529–8536 (2014)CrossRefPubMedGoogle Scholar
  38. 38.
    C. Houée-Lévin et al., Exploring oxidative modifications of tyrosine: an update on mechanisms of formation, advances in analysis and biological consequences. Free Radical Res. 49(4), 347–373 (2015)CrossRefGoogle Scholar
  39. 39.
    T. Michon et al., Horseradish peroxidase oxidation of tyrosine-containing peptides and their subsequent polymerization: a kinetic study. Biochemistry 36(28), 8504–8513 (1997)CrossRefPubMedGoogle Scholar
  40. 40.
    F. Cavalieri et al., Sono-assembly of nanostructures via tyrosine–tyrosine coupling reactions at the interface of acoustic cavitation bubbles. Materials Horizons 3, 563–567 (2016)CrossRefGoogle Scholar
  41. 41.
    M. Ashokkumar, T.J. Mason, Sonochemistry. Kirk-Othmer Encycl. Chem. Technol. y On-Line, Wiley Interscience (2007) Google Scholar
  42. 42.
    J. Berthelot, Y. Benammar, C. Lange, A mild and efficient sonochemical bromination of alkenes using tetrabutylammonium tribromide. Tetrahedron Lett. 32(33), 4135–4136 (1991)CrossRefGoogle Scholar
  43. 43.
    S.K. Bhangu, M. Ashokkumar, Theory of sonochemistry. Top. Curr. Chem. 374(4), 56 (2016)CrossRefGoogle Scholar
  44. 44.
    M.H. Entezari, C. Pétrier, A combination of ultrasound and oxidative enzyme: sono-enzyme degradation of phenols in a mixture. Ultrason. Sonochem. 12(4), 283–288 (2005)CrossRefPubMedGoogle Scholar
  45. 45.
    S. Okouchi, O. Nojima, T. Arai, Cavitation-induced degradation of phenol by ultrasound. Water Sci. Technol. 26(9–11), 2053–2056 (1992)CrossRefGoogle Scholar
  46. 46.
    C. Petrier et al., Sonochemical degradation of phenol in dilute aqueous solutions: comparison of the reaction rates at 20 and 487 kHz. J. Phys. Chem. 98(41), 10514–10520 (1994)CrossRefGoogle Scholar
  47. 47.
    N. Serpone et al., Sonochemical oxidation of phenol and three of its intermediate products in aqueous media: catechol, hydroquinone, and benzoquinone. Kinetic and mechanistic aspects. Res. Chem. Intermed. 18(2), 183–202 (1992)CrossRefGoogle Scholar
  48. 48.
    C. Wu et al., Photosonochemical degradation of phenol in water. Water Res. 35(16), 3927–3933 (2001)CrossRefPubMedGoogle Scholar
  49. 49.
    S.K. Bhangu, M. Ashokkumar, F. Cavalieri, A simple one-step ultrasonic route to synthesize antioxidant molecules and fluorescent nanoparticles from phenol and phenol-like molecules. ACS Sustain. Chem. Eng. 5(7), 6081–6089 (2017)CrossRefGoogle Scholar
  50. 50.
    F.F. Bruno et al., Polymerization of water-soluble conductive polyphenol using horseradish peroxidase. J. Macromol. Sci. Part A 38(12), 1417–1426 (2001)CrossRefGoogle Scholar
  51. 51.
    P.K. Jha, G.P. Halada, The catalytic role of uranyl in formation of polycatechol complexes. Chem. Cent. J. 5(1), 12 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    D.A. Malencik et al., Dityrosine: preparation, isolation, and analysis. Anal. Biochem. 242(2), 202–213 (1996)CrossRefPubMedGoogle Scholar
  53. 53.
    G.J. Smith, T.G. Haskell, The fluorescent oxidation products of dihydroxyphenylalanine and its esters. J. Photochem. Photobiol., B 55(2), 103–108 (2000)CrossRefGoogle Scholar
  54. 54.
    J. Chandrapala et al., Effects of ultrasound on the thermal and structural characteristics of proteins in reconstituted whey protein concentrate. Ultrason. Sonochem. 18(5), 951–957 (2011)CrossRefPubMedGoogle Scholar
  55. 55.
    A.K. Goard, E.K. Rideal, CCXXI—The surface tensions of aqueous phenol solutions. Part II. Activity and surface tension. J. Chem. Soc. Trans. 127, 1668–1676 (1925)CrossRefGoogle Scholar
  56. 56.
    R.Y. Tsien, The green fluorescent protein. Annu. Rev. Biochem. 67(1), 509–544 (1998)CrossRefPubMedGoogle Scholar
  57. 57.
    S.K. Bhangu et al., Sono-transformation of tannic acid into biofunctional ellagic acid micro/nanocrystals with distinct morphologies. Green Chem. 20, 816–821 (2018)CrossRefGoogle Scholar
  58. 58.
    I. Mueller-Harvey, Analysis of hydrolysable tannins. Anim. Feed Sci. Technol. 91(1), 3–20 (2001)CrossRefGoogle Scholar
  59. 59.
    L. Pouységu et al., Synthesis of ellagitannin natural products. Nat. Prod. Rep. 28(5), 853–874 (2011)CrossRefPubMedGoogle Scholar
  60. 60.
    H. Ejima et al., One-step assembly of coordination complexes for versatile film and particle engineering. Science 341(6142), 154–157 (2013)CrossRefPubMedGoogle Scholar
  61. 61.
    S. Quideau et al., Plant polyphenols: chemical properties, biological activities, and synthesis. Angew. Chem. Int. Ed. 50(3), 586–621 (2011)CrossRefGoogle Scholar
  62. 62.
    N. Bertleff-Zieschang et al., Biofunctional metal–phenolic films from dietary flavonoids. Chem. Commun. 53(6), 1068–1071 (2017)CrossRefGoogle Scholar
  63. 63.
    A. Brune, B. Schink, Phloroglucinol pathway in the strictly anaerobic Pelobacter acidigallici: fermentation of trihydroxybenzenes to acetate via triacetic acid. Arch. Microbiol. 157(5), 417–424 (1992)CrossRefGoogle Scholar
  64. 64.
    L. Mingshu et al., Biodegradation of gallotannins and ellagitannins. J. Basic Microbiol. 46(1), 68–84 (2006)CrossRefGoogle Scholar
  65. 65.
    Q. Sun, J. Heilmann, B. König, Natural phenolic metabolites with anti-angiogenic properties–a review from the chemical point of view. Beilstein J. Org. Chem. 11, 249 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    S. Kaur Bhangu, M. Ashokkumar, J. Lee, Ultrasound assisted crystallization of paracetamol: crystal size distribution and polymorph control. Cryst. Growth Des. 16(4), 1934–1941 (2016)CrossRefGoogle Scholar
  67. 67.
    V.S. Nalajala, V.S. Moholkar, Investigations in the physical mechanism of sonocrystallization. Ultrason. Sonochem. 18(1), 345–355 (2011)CrossRefPubMedGoogle Scholar
  68. 68.
    H.-M. Zhang et al., Research progress on the anticarcinogenic actions and mechanisms of ellagic acid. Cancer Biol. Med. 11(2), 92 (2014)PubMedPubMedCentralGoogle Scholar
  69. 69.
    N. Wang et al., Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. Breast Cancer Res. Treat. 134(3), 943–955 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    L. Tang et al., Inhibition of angiogenesis and invasion by DMBT is mediated by downregulation of VEGF and MMP-9 through Akt pathway in MDA-MB-231 breast cancer cells. Food Chem. Toxicol. 56, 204–213 (2013)CrossRefPubMedGoogle Scholar

Copyright information

© The Author(s), under exclusive licence to Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate School of Humanities and Sustainable System SciencesOsaka Prefecture UniversityOsakaJapan
  2. 2.Department of Chemical EngineeringThe University of MelbourneParkvilleAustralia

Personalised recommendations