Abstract
Nanogels combine the favourable properties of hydrogels with those of colloids. They can be soft and conformable, stimuli-responsive and highly permeable, and can expose a large surface with functional groups for conjugation to small and large molecules, and even macromolecules. They are among the very few systems that can be generated and used as aqueous dispersions. Nanogels are emerging materials for targeted drug delivery and bio-imaging, but they have also shown potential for water purification and in catalysis. The possibility of manufacturing nanogels with a simple process and at relatively low cost is a key criterion for their continued development and successful application. This paper highlights the most important structural features of nanogels related to their distinctive properties, and briefly presents the most common manufacturing strategies. It then focuses on synthetic approaches that are based on the irradiation of dilute aqueous polymer solutions using high-energy photons or electron beams. The reactions constituting the basis for nanogel formation and the approaches for controlling particle size and functionality are discussed in the context of a qualitative analysis of the kinetics of the various reactions.
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28 September 2016
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References
IUPAC (1997) Compendium of Chemical Terminology, 2nd ed. (the “Gold Book”). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford. XML on-line corrected version: http://goldbook.iupac.org (2006) created by M. Nic, J. Jirat, B. Kosata; updates compiled by A. Jenkins
Motornov M, Roiter Y, Tokarev I, Minko S (2010) Stimuli-responsive nanoparticles, nanogels and capsules for integrated multifunctional intelligent systems. Prog Polym Sci 35:174–211
Ricka J, Tanaka T (1984) Swelling of ionic gels: quantitative performance of the Donnan theory. Macromolecules 17:2916–2921
Akiyoshi K, Kobayashi S, Shichibe S, Mix D, Baudys M, Kim SW, Sunamoto J (1998) Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin. J Control Release 54(3):313–320
Chen Y, Ballard N, Bon SAF (2013) Waterborne polymer nanogels non-covalently crosslinked by multiple hydrogen bond arrays. Polym Chem 4:387–392
Lim C-K, Singh A, Heo J, Kim D, Lee KE, Jeon H, Koh J, Kwon I-C, Kim S (2013) Gadolinium-coordinated elastic nanogels for in vivo tumor targeting and imaging. Biomaterials 34:6846–6852
López-León T, Carvalho ELS, Seijo B, Ortega-Vinuesa JL, Bastos-González D (2005) Physicochemical characterization of chitosan nanoparticles: electrokinetic and stability behaviour. J Colloid Interf Sci 283:344–351
Israelachvili JN (2011) Intermolecular and surface forces, 3rd edn. Academic Press, San Diego
Picone P, Ditta LA, Sabatino MA, Militello V, San Biagio PL, Di Giacinto ML, Cristaldi L, Nuzzo D, Dispenza C, Giacomazza D, Di Carlo M (2016) Ionizing radiation-engineered nanogels as insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer’s disease. Biomaterials 80:179–194
Brown W, Nicolai T (1993) Dynamic light scattering: the method and some applications. Ed. Clarendon Press, Oxford
Wyatt PJ (1993) Light scattering and the absolute characterization of macromolecules. Anal Chim Acta 272:1–40
Maya S, Sarmento B, Nair A, Rejinold NS, Nair SV, Jayakumar R (2013) Smart stimuli sensitive nanogels in cancer drug delivery and imaging: a review. Curr Pharm Des 19(41):7203–7218
Shen X, Zhang L, Jiang X, Hu Y, Guo J (2007) Reversible surface switching of nanogel triggered by external stimuli. Angew Chem Int Ed 46:7104–7107
Du J-Z, Sun T-M, Song W-J, Wu J, Wang JA (2010) Tumor-acidity-activated charge-conversional nanogel as an intelligent vehicle for promoted tumoral-cell uptake and drug delivery. Angew Chem Int Ed 49:3621–3626
Zha L, Banik B, Alexis F (2011) Stimulus responsive nanogels for drug delivery. Soft Matter 7:5908–5916
Bromberg LE, Ron ES (1998) Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv Drug Deliv Rev 31:197–221
Gandhi SS, Yan H, Kim C (2014) Thermoresponsive gelatin nanogels. ACS Macro Lett 3:1210–1214
Xu S, Olenyuk BZ, Okamoto CT, Hamm-Alvarez SF (2013) Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv Drug Deliv Rev 65(1):121–138
Lei Ye (ed) (2013) Molecular imprinting: principles and applications of micro- and nanostructured polymers. CRC Press
Carboni D, Flavin K, Servant A, Gouverneur V, Resmini M (2008) The first example of molecularly imprinted nanogels with aldolase type I activity. Chemistry 14(23):7059–7065
Pan G, Guo Q, Cao C, Yang H, Li B (2013) Thermo-responsive molecularly imprinted nanogels for specific recognition and controlled release of proteins. Soft Matter 9:3840–3850
Varga I, Szalai I, Mészaros R, Gilányi T (2006) Pulsating pH-responsive nanogels. J Phys Chem B 110(41):20297–20301
Sakai T, Yoshida R (2004) Self-oscillating nanogel particles. Langmuir 20(4):1036–1038
Wu W, Zhou S (2010) Hybrid micro-/nanogels for optical sensing and intracellular imaging. Nano Rev 1:5730
Kondo K, Kaji N, Toita S, Okamoto Y, Tokeshi M, Akiyoshi K, Baba Y (2010) DNA separation by cholesterol-bearing pullulan nanogels. Biomicrofluidics 4(3):32210–32218
Akl MA, Sarhan AA, Shoueir KR, Atta AM (2013) Application of crosslinked ionic poly(vinyl alcohol)nanogel as adsorbents for water treatment. J Dispers Sci Technol 34(10):1399–1408
Resmini M, Flavin K, Carboni D (2012) Microgels and nanogels with catalytic activity. Top Curr Chem 325:307–342
Kuroda K, Fujimoto K, Sunamoto J, Akiyoshi K (2002) Hierarchical self-assembly of hydrophobically modified pullulan in water: gelation by networks of nanoparticles. Langmuir 18(10):3780–3786
Nakai T, Hirakura T, Sakurai Y, Shimoboji T, Ishigai M, Akiyoshi K (2012) Injectable hydrogel for sustained protein release by salt-induced association of hyaluronic acid nanogel. Macromol Biosci 12(4):475–483
Li Y, Ye Z, Shen L, Xu Y, Zhu A, Wu P, An Z (2016) Formation of multidomain hydrogels via thermally induced assembly of pisa-generated triblock terpolymer nanogels. Macromolecules 49(8):3038–3048
Xia L-W, Xie R, Ju X-J, Wang W, Chen Q, Chu L-Y (2013) Nano-structured smart hydrogels with rapid response and high elasticity. Nat Commun 4:2226–2236
Luo F, Xie R, Liu Z, Ju X-J, Wang W, Lin S, Chu L-Y (2015) Smart gating membranes with in situ self-assembled responsive nanogels as functional gates. Sci Rep 5:14708–14721
Reese CE, Mikhonin AV, Kamenjicki M, Tikhonov A, Asher SA (2004) Nanogel nanosecond photonic crystal optical switching. J Am Chem Soc 126(5):1493–1496
Tian L, Liu K-K, Fei M, Tadepalli S, Cao S, Geldmeier JA, Tsukruk VV, Singamaneni S (2016) Plasmonic nanogels for unclonable optical tagging. ACS Appl Mater Interfaces 8(6):4031–4041
Saez-Martinez V, Olalde B, Juan MJ, Jurado MJ, Garagorri N, Obieta I (2010) Novel bioactive scaffolds incorporating nanogels as potential drug eluting devices. J Nanosci Nanotechnol 10(4):2826–2832
Oh JK, Drumright R, Siegwart DJ, Matyjaszewski K (2008) The development of microgel/nanogels for drug delivery applications. Prog Polym Sci 33(4):448–477
Kabanov AV, Vinogradov SV (2009) Nanogels as pharmaceutical carriers: finite networks of infinite capabilities. Angew Chem Int Ed Engl 48(30):5418–5429
Sanson N, Rieger J (2010) Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization. Polym Chem 1:965–977
Zhang X, Malhotra S, Molina M, Haag R (2015) Micro- and nanogels with labile crosslinks—from synthesis to biomedical applications. Chem Soc Rev 44:1948–1973
Ulański P, Rosiak JM (2004) Polymeric Nano/Microgels. In: Nalwa HS (ed) Encyclopedia of nanoscience and Nanotechnology, vol VIII, pp 845–871, ISBN 1-58883-001-2. American Scientific Publishers, Stevenson Ranch
Lipomi DJ, Martinez RV, Cademartiri L, Whitesides GM (2012) Soft lithographic approaches to nanofabrication, chapter 7.11. In: Matyjaszewski K and Möller M (eds) Polymer science: a comprehensive reference, 1st edn. Elsevier, Amsterdam, pp 211–231
Rolland JP, Maynor BW, Euliss LE, Exner AE, Denison GM, DeSimone JM (2005) Direct fabrication and harvesting of monodisperse, shape-specific nanobiomaterials. J Am Chem Soc 127(28):10096–10100
Omichi M, Marui H, Takano K, Tsukuda S, Sugimoto M, Kuwabata S, Seki S (2012) Temperature-responsive one-dimensional nanogels formed by the cross-linker-aided single particle nanofabrication technique. ACS Appl Mater Interfaces 4(10):5492–5497
Zhang H, Tumarkin E, Sullan RMA, Walker GC, Kumacheva E (2007) Exploring microfluidic routes to microgels of biological polymers. Macromol Rapid Commun 28(5):527–538
Bazban-Shotorbani S, Dashtimoghadam E, Karkhaneh A, Hasani-Sadrabadi MM, Jacob KI (2016) Microfluidic directed synthesis of alginate nanogels with tunable pore size for efficient protein delivery. Langmuir 32(19):4996–5003
Nesvadba P (2012) Radical polymerization in industry. In: Chatgilialoglu C, Studer A (eds) Encyclopedia of radicals in chemistry, biology and materials. John Wiley & Sons, Inc, New York
Oh JK, Bencherif SA, Matyjaszewski K (2009) Polymer atom transfer radical polymerization in inverse miniemulsion: a versatile route toward preparation and functionalization of microgels/nanogels for targeted drug delivery applications. Polymer 50(19):4407–4423
Medeiros SF, Santos AM, Fessi H, Elaissari A (2010) Synthesis of biocompatible and thermally sensitive poly(N-vinylcaprolactam) nanogels via inverse miniemulsion polymerization: effect of the surfactant concentration. J Polym Sci A Polym Chem 48:3932–3941
Klinger D, Aschenbrenner EM, Weiss KC, Landfester K (2012) Enzymatically degradable nanogels by inverse miniemulsion copolymerization of acrylamide with dextran methacrylates as crosslinkers. Polym Chem 3:204–216
Sarika PR, James NR (2015) Preparation and characterisation of gelatin–gum arabic aldehyde nanogels via inverse miniemulsion technique. Int J Biol Macromol 76:181–187
Blackburn WH, Lyon LA (2008) Size controlled synthesis of monodispersed, core/shell nanogels. Colloid Polym Sci 286(5):563–569
Muller AHE, Matyjaszewski K (eds) (2010) Controlled and living polymerizations from mechanisms to applications. Wiley-VCH Verlag GmbH, Weinheim
Destarac M (2010) Controlled Radical Polymerization: industrial stakes, obstacles and achievements. Macromol React Eng 4(3–4):165–179
Lupitskyya R, Minko S (2010) Robust synthesis of nanogel particles by an aggregation-crosslinking method. Soft Matter 6:4396–4402
Li Y, Maciel D, Rodrigues J, Shi X, Tomás H (2015) Biodegradable polymer nanogels for drug/nucleic acid delivery. Chem Rev 115(16):8564–8608
Lee JI, Kim HS, Yoo HS (2009) DNA nanogels composed of chitosan and Pluronic with thermo-sensitive and photo-crosslinking properties. Int J Pharma 373(1–2):93–99
Zubareva A, Ilyina A, Prokhorov A, Kurek D, Efremov M, Varlamov V, Senel S, Ignatyev P, Svirshchevskaya E (2013) Characterization of protein and peptide binding to nanogels formed by differently charged chitosan derivatives. Molecules 18(7):7848–7864
Siqueira Franco Picone C, Lopes Cunha R (2013) Chitosan–gellan electrostatic complexes: influence of preparation conditions and surfactant presence. Carbohydr Polym 94(1):695–703
Hiramoto S, Amano Y, Sato M, Suzuki Y, Shinohara M, Emoto S, Yamaguchi H, Ishigami H, Sakai Y, Kitayama J, Ito T (2016) Production of cisplatin-incorporating hyaluronan nanogels via chelating ligand-metal coordination. Bioconjug Chem 27(3):504–508
Vo CD, Kuckling D, Adler H-JP, Schonhoff M (2002) Preparation of thermosensitive nanogels by photo-cross-linking. Colloid Polym Sci 280:400–409
Dispenza C, Grimaldi N, Sabatino MA, Soroka IL, Jonsson M (2015) Radiation-engineered functional nanoparticles in aqueous system. J Nanosci Nanotech 15(5):3445–3467
Rosiak JM (1994) Radiation formation of hydrogels for drug delivery. J Control Release 31(1):9–19
Charlesby A (1960) Atomic radiation and polymers. Pregamon Press, Oxford
Charlesby A, Alexander P (1955) Reticulation of polymers in aqueous solution by γ-rays. J Chim Phys PCB 52:699–709
Charlesby A, Alexander P (1957) Effect of X-rays and γ-rays on synthetic polymers in aqueous solution. J Polym Sci 23:355–375
Sakurada I, Ikada Y (1996) Effects of Gamma Radiation on Polymer in Solution (IX): a turbidimetric study on solution of poly(vinyl alcohol) irradiated below critical concentration for gel-formation (Special Issue on Physical, Chemical and Biological Effects of Gamma Radiation, VII). Bull Inst Chem Res Kyoto Univ 44(1):66–73
Schnabel W, Borgwardt U (1969) Über die vernetzung von polyäthylenoxid in lösung unter der einwirkung von 60CO-γ-strahlen. Makromol Chem 123:73–79
Ulanski P, Rosiak JM (1999) The use of radiation technique in the synthesis of polymeric nanogels. Nucl Instrum Methods Phys Res B 151(1–4):356–360
Kadlubowski S (2014) Radiation-induced synthesis of nanogels based on poly(N-vinyl-2-pyrrolidone)—a review. Radiat Phys Chem 102:29–39 and references herein
Ulanski P, Janik I, Rosiak JM (1998) Radiation formation of polymeric nanogels. Radiat Phys Chem 52:289–294
Ulanski P, Kadlubowski S, Rosiak JM (2002) Synthesis of poly (acrylic acid) nanogels by preparative pulse radiolysis. Radiat Phys Chem 63(3–6):533–537
Kadlubowski S, Grobelny J, Olejniczak W, Cichomski M, Ulanski P (2003) Pulses of fast electrons as a tool to synthesize poly (acrylic acid) nanogels. Intramolecular cross-linking of linear polymer chains in additive-free aqueous solution. Macromolecules 36(7):2484–2492
Arndt K-F, Schmidt T, Reichelt R (2001) Thermo-sensitive poly(methyl vinyl ether) micro-gel formed by high energy radiation. Polymer 42:6785–6791
Querner C, Schmidt T, Arndt K-F (2004) Characterization of structural changes of poly(vinyl methyl ether) gamma-irradiated in diluted aqueous solutions. Langmuir 20(7):2883–2889
Schmidt T, Janik I, Kadlubowski S, Ulanski P, Rosiak JM, Reichelt R, Arndt K-F (2005) Pulsed electron beam irradiation of dilute aqueous poly (vinyl methyl ether) solutions. Polymer 46(23):9908–9918
El-Rehim HAA (2005) Swelling of radiation crosslinked acrylamide-based microgels and their potential applications. Radiat Phys Chem 74(2):111–117
Picos-Corrales LA, Licea-Claveríe A, Arndt K-F (2012) Stimuli-responsive nanogels by e-beam irradiation of dilute aqueous micellar solutions: Nanogels with pH controlled LCST. Chapter 7: Polymer Nanotechnology. In: Nanotechnology 2012: advanced materials, CNTs, particles, films and composites, vol 1. NSTI publication
Chmielewski AG, Haji-Saeid M, Shamshad Ahmed S (2005) Progress in radiation processing of polymers. Nucl Instrum Methods Phys Res Sect B 236(1):44–54
Sabatino MA, Bulone D, Veres M, Spinella A, Spadaro G, Dispenza C (2013) Structure of e-beam sculptured poly(N-vinylpyrrolidone) networks across different length-scales, from macro to nano. Polymer 54(1):54–64
Dispenza C, Sabatino MA, Grimaldi N, Spadaro G, Bulone D, Bondì ML, Adamo G, Rigogliuso S (2012) Large-scale radiation manufacturing of hierarchically assembled nanogels. Chem Eng Trans 27:229C–234C
Dispenza C, Sabatino MA, Grimaldi N, Bulone D, Bondi ML, Casaletto MP, Rigogliuso S, Adamo G, Ghersi G (2012) Minimalism in radiation synthesis of biomedical functional nanogels. Biomacromolecules 13:1805–1817
Adamo G, Grimaldi N, Sabatino MA, Walo M, Dispenza C, Ghersi G (2016) E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting strategies. Biol Chem. doi:10.1515/hsz-2016-0255
Spinks JWT, Woods RJ (1990) An introduction to radiation chemistry. Wiley-Interscience, Wiley, New York
Alfassi ZB (1999) General aspects of the chemistry of radicals. Wiley, New York
Dispenza C, Sabatino M, Grimaldi N, Mangione M, Walo M, Murugan E, Jonsson M (2016) On the origin of functionalisation in one-pot radiation synthesis of nanogels from aqueous polymer solutions. RSC Adv 6(4):2582–2591
Plonka A (1991) Developments in dispersive kinetics. Prog React Kinet 16:157–333
Jeszka JK, Kadlubowski S, Ulanski P (2006) Monte Carlo simulations of nanogels formation by intramolecular recombination of radicals on polymer chain. Dispersive kinetics controlled by chain dynamics. Macromolecules 39:857–870
An JC, Weaver A, Kim B, Barkatt A, Poster D, Vreeland WN, Silverman J, Al-Sheikhly M (2011) Radiation-induced synthesis of poly(vinylpyrrolidone) nanogel. Polymer 52:5746–5755
Schmitz KS, Wang B, Kokufuta E (2001) Mechanism of microgel formation via cross-linking of polymers in their dilute solutions: mathematical explanation with computer simulations. Macromolecules 34:8370–8377
Brasch U, Burchard W (1996) Preparation and solution properties of microhydrogels from poly(vinyl alcohol). Macromol Chem Phys 197:223–235
Kadlubowski S, Ulanski P, Rosiak JM (2012) Synthesis of tailored nanogels by means of two-stage irradiation. Polymer 53:1985–1991
Gorlich W, Schnabel W (1973) Untersuchungen uber dei Eiflu der Ladungsdichte aur die gegenseitige Desaktvierung von Polyion-Mackroradikalen. Die Macromoleculare Chemie 164:225–235
Grimaldi N, Sabatino MA, Przybytniak G, Kaluska I, Bondi’ ML, Bulone D, Alessi S, Spadaro G, Dispenza C (2014) High-energy radiation processing, a smart approach to obtain PVP-graft-AA nanogels. Radiat Phys Chem 94:76–79
Henke A, Kadłubowski S, Ulański P, Arndt K-F, Rosiak JM (2005) Radiation-induced cross-linking of polyvinylpyrrolidone-poly(acrylic acid) complexes. Nucl Instr Meth Phys Res B 236:391–398
El-Rehim HAA, Hegazy ESA, Hamed AA, Swilem AE (2013) Controlling the size and swellability of stimuli-responsive polyvinylpyrrolidone–poly (acrylic acid) nanogels synthesized by gamma radiation-induced template polymerization. Eur Polym J 49(3):601–612
Adamo G, Grimaldi N, Campora S, Sabatino MA, Dispenza C, Ghersi G (2014) Glutathione-sensitive nanogels for drug release. Chem Eng Trans 38:457–462
Dispenza C, Adamo G, Sabatino MA, Grimaldi N, Bulone D, Bondì ML, Rigogliuso S, Ghersi G (2014) Oligonucleotides-decorated-poly(N-vinyl pyrrolidone) nanogels for gene delivery. J Appl Polym Sci 131(2):239774–239780
El-Rehim HAA, Swilem AE, Klingner A, Hegazy ESA, Hamed AA (2013) Developing the potential ophthalmic applications of pilocarpine entrapped into polyvinylpyrrolidone-poly(acrylic acid) nanogel dispersions prepared by γ radiation 2013. Biomacromolecules 14(3):688–698
Lorenzo A, Picos-Corrales LA, Angel Licea-Claveríe A, Arndt K-F (2014) React Funct Polym 75:31–40
Meléndez-Orti HI, Peralta RD, Bucio E, Zerrweck-Maldonado L (2014) Preparation of stimuli-responsive nanogels of poly [2-(dimethylamino) ethyl methacrylate] by heterophase and microemulsion polymerization using gamma radiation Polym. Eng Sci 54:1625–1631
Yusof H, Naurah MI, Liyana MAN (2014) Polyethylene glycol diacrylate microgels from irradiated micelles. Adv Mater Res 1024:316–319
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This article is part of the Topical Collection “Applications of Radiation Chemistry”; edited by Margherita Venturi, Mila D’Angelantonio.
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Dispenza, C., Spadaro, G. & Jonsson, M. Radiation Engineering of Multifunctional Nanogels. Top Curr Chem (Z) 374, 69 (2016). https://doi.org/10.1007/s41061-016-0071-x
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DOI: https://doi.org/10.1007/s41061-016-0071-x