Behavior of hybrid thermosensitive nanosystem dextran-graft-PNIPAM/gold nanoparticles: characterization within LCTS

  • N. Kutsevol
  • A. GlamazdaEmail author
  • V. Chumachenko
  • Yu. Harahuts
  • S. G. Stepanian
  • A. M. Plokhotnichenko
  • V. A. Karachevtsev
Research Paper


Thermally responsive polymers based on poly (N-isopropylacrylamide) (PNIPAM) with lower critical solution temperature (LCST) in the region of physiological temperatures become a subject of a study as promising material for biomedical application. In the present work, the star-like dextran-graft-PNIPAM with incorporated gold nanoparticles (AuNPs) in water suspension were studied by quasi-elastic light scattering (QELS), transmission electron microscopy (TEM), and spectroscopic methods in the temperature range around LCST. The analysis of QELS results revealed the individual polymer macromolecules with incorporated inside AuNPs and their aggregates, which demonstrate the LCST near 34 °C with the collapse of individual macromolecules and polymer aggregates too. The absorption spectroscopy measurements showed that the polymer structure is reversible at LCST and heating of polymer/AuNP nanosystems from room temperatures to LCTS does not accompany with a release of AuNPs from the polymer matrix. Raman spectra of nanohybrids were measured below and above LCTS and analyzed in details by employing DFT calculations. Two intense bands in the region 50–300-cm−1 region were observed for the first time. They were assigned to the stretching vibrations of Au-Au and Au-O (NIPAM) bonds. The presented work shows that the synthesized polymer with AuNPs has high stability going through LCST encouraging their use as a perspective system for drug delivery strategy.

Graphical abstract


PNIPAM Thermoresponsive polymer Gold nanoparticles Surface plasmon resonance Quasi-elastic light scattering Raman spectroscopy DFT calculation Colloids Biomedical applications 



A.G. would like to thank to Dr. I. Voloshin for the fruitful discussions. Authors thank to Dr. M. Rawiso and C. Blank from Institute Charles Sadron (Strasbourg, France) for the SEC and TEM characterization of polymer sample.


Publications are based on the research provided by the grant support of the State Fund For Fundamental Research (project Ф76/64-2017 “New multifunctional hybrid nanocomposites for photodynamic chemotherapy of tumor cells”). This work has been partially supported by National Academy of Sciences of Ukraine (Grant No. 15/18-H within the program “Fundamental Problems of the creation of new Nanomaterials and Nanotechnology” and Grant No. 0114U001070).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11051_2018_4331_MOESM1_ESM.doc (392 kb)
ESM 1 (DOC 392 kb)


  1. Abadeer NS, Murphy CJ (2016) Recent progress in Cancer thermal therapy using gold nanoparticles. J Phys Chem C 120(9):4691–4716. CrossRefGoogle Scholar
  2. Ahmed Z, Gooding EA, Pimenov KV, Wang L, Asher SA (2009) UV resonance Raman determination of molecular mechanism of poly (N-isopropylacrylamide) volume phase transition. J Phys Chem B 113(13):4248–4256. CrossRefGoogle Scholar
  3. Andrae D, Haeussermann U, Dolg M, Stoll H, Preuss H (1990) Energy-adjusted ab initio pseudopotentials for the 2nd and 3rd row transition-elements. Theor Chem Accounts 77(2):123–141. CrossRefGoogle Scholar
  4. Arvizo R, Bhattacharya R, Mukherjee P (2010) Gold nanoparticles: opportunities and challenges in nanomedicine. Expert Opin Drug Deliv 7(6):753–763. CrossRefGoogle Scholar
  5. Assadollahzadeh B, Schwerdtfeger P (2009) A systematic search for minimum structures of small gold clusters Aun (n=2–20) and their electronic properties. J Chem Phys 131(6):064306. CrossRefGoogle Scholar
  6. Becke AD (1988) Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev B 38(6):3098–3100. CrossRefGoogle Scholar
  7. Bezuglyi M, Kutsevol N, Rawiso M, Bezugla T (2012) Water-soluble branched copolymers dextran-polyacrylamide and their anionic Derivates as matrices for metal nanoparticles in-situ synthesis. Chemik 8(66):862–867Google Scholar
  8. Bürgi T (2015) Properties of the gold–Sulphur interface: from self-assembled monolayers to clusters. Nanoscale 7:15553–15567. CrossRefGoogle Scholar
  9. Cai W, Gao T, Hong H, Sun J (2008) Applications of gold nanoparticles in cancer nanotechnology. Nanotechnol Sci Appl 1:17–32. CrossRefGoogle Scholar
  10. Chatterjee DK, Diagaradjane P, Krishnan S (2011) Nanoparticle-mediated hyperthermia in cancer therapy. Ther Deliv 2(8):1001–1014. CrossRefGoogle Scholar
  11. Chumachenko V, Kutsevol N, Harahuts Y, Rawiso M, Marinin A, Bulavin L (2017) Star-like dextran-graft-PNiPAM copolymers. Effect of internal molecular structure on the phase transition. J Mol Liq 235:77–82. CrossRefGoogle Scholar
  12. Cooperstein MA, Canavan HE (2013) Assessment of cytotoxicity of (N-isopropyl acrylamide) and poly (N-isopropyl acrylamide)-coated surfaces. Biointerphases 8:19. CrossRefGoogle Scholar
  13. Dreaden EC, Austin LA, Mackey MA, El-Sayed MA (2012) Size matters: gold nanoparticles in targeted cancer drug delivery. Ther Deliv 3(4):457–478. CrossRefGoogle Scholar
  14. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09, Revision A.02. Gaussian, Inc., WallingfordGoogle Scholar
  15. Gruene P, Rayner DM, Redlich B, van der Meer AFG, Lyon JT, Meijer G, Fielicke A (2008) Structures of neutral Au7, Au19, and Au20 clusters in the gas phase. Science 321(5889):674–676. CrossRefGoogle Scholar
  16. Haiss W, Thanh NTK, Aveyard J, Fernig DG (2007) Determination of size and concentration of gold Nanoparticles from UV-vis spectra. Anal Chem 79:4215–4221. CrossRefGoogle Scholar
  17. Halperin A, Kröger M, Winnik FM (2015) Poly (N-isopropylacrylamide) phase diagrams: fifty years of research. Angew Chem Int Ed 54:15342–15367. CrossRefGoogle Scholar
  18. Han D-M, Zhang QM, Serpe MJ (2015) Poly (N-isopropylacrylamide)-co-(acrylic acid) microgel/ag nanoparticle hybrids for the colorimetric sensing of H2O2. Nanoscale 7:2784–2789. CrossRefGoogle Scholar
  19. Haume K, Rosa S, Grellet S, Śmiałek MA, Butterworth KT, Solov’yov AV, Prise KM, Golding J, Mason NJ (2016) Gold nanoparticles for cancer radiotherapy: a review. Cancer Nanotechnol 7:8–28. CrossRefGoogle Scholar
  20. Huang X, El-Sayed MA (2010) Gold nanoparticles: optical properties and implementations in cancer diagnosis and photothermal therapy. J Adv Res 1(1):13–28. CrossRefGoogle Scholar
  21. Huff TB, Tong L, Zhao Y, Hansen MN, Cheng J-X, Wei A (2007) Hyperthermic effects of gold nanorods on tumor cells. Nanomedicine 2(1):125–132. CrossRefGoogle Scholar
  22. Jain K, Vedarajan R, Watanabe M, Ishikiriyama M, Matsumi N (2015) Tunable LCST behavior of poly (N-isopropylacrylamide/ionic liquid) copolymers. Polym Chem 6:6819–6825. CrossRefGoogle Scholar
  23. Karachevtsev VA, Zarudnev ES, Stepanian SG, Glamazda AY, Karachevtsev MV, Adamowicz L (2010) Raman spectroscopy and theoretical characterization of Nanohybrids of porphyrins with carbon nanotubes. J Phys Chem C 114:16215–16222. CrossRefGoogle Scholar
  24. Karg M, Pastoriza–Santos I, Perez–Juste J, Hellweg T, Liz-Marzan LM (2007) Nanorod–coated PNIPAM Microgels: thermoresponsive optical properties. Small 3:1222–1229. CrossRefGoogle Scholar
  25. Kennedy LC, Bickford LR, Lewinski NA, Coughlin AJ, Hu Y, Day ES, West JL, Drezek RA (2010) A new era for Cancer treatment: gold-nanoparticle mediated thermal therapies. Small 7(2):1–15. CrossRefGoogle Scholar
  26. Kreibig U, Vollmer M (1995) Optical properties of metal clusters. Springer, New YorkCrossRefGoogle Scholar
  27. Kutsevol NV, Chumachenko VA, Rawiso M, Shkodich VF, Stoyanov OV (2015) Star-like polymers dextran-polyacrylamide: the prospects of application for nanotechnology. J Struct Chem 56(5):959–966. CrossRefGoogle Scholar
  28. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37(2):785–789. CrossRefGoogle Scholar
  29. Li J, He WD, Sun XL (2007) Preparation of poly (styrene-b- N-isopropylacrylamide) micelles surface-linked with gold nanoparticles and thermo-responsive ultraviolet–visible absorbance. J Polym Sci A Polym Chem 45:5156–5163. CrossRefGoogle Scholar
  30. Lima LH, Morales Y, Cabral T (2016) Ocular biocompatibility of poly-N-Isopropylacrylamide (pNIPAM). J Ophthalmol 2016:5356371. CrossRefGoogle Scholar
  31. Manikas AC, Aliberti A, Causa F, Battista E, Netti PA (2015) Thermoresponsive PNIPAAm hydrogel scaffolds with encapsulated AuNPs show high analyte-trapping ability and tailored plasmonic properties for high sensing efficiency. J Mater Chem B 3:53–58. CrossRefGoogle Scholar
  32. Park JY, Kim JS, Nam YS (2013) Mussel-inspired modification of dextran for protein-resistant coatings of titanium oxide. Carbohydr Polym 97(2):753–757. CrossRefGoogle Scholar
  33. Pelton R (2010) Poly (N-isopropylacrylamide) (PNIPAM) is never hydrophobic. J Colloid Interface Sci 348(2):673–674. CrossRefGoogle Scholar
  34. Provencher S (1982) CONTIN: a general purpose constrained regularization program for inverting noisy linear algebraic and integral equations. Comput Phys Commun 27:229–242. CrossRefGoogle Scholar
  35. Scotti A, Liu W, Hyatt JS, Herman ES, Choi HS, Kim JW, Lyon LA, Gasser U, Fernandez-Nieves A (2015) The CONTIN algorithm and its application to determine the size distribution of microgel suspensions. J Chem Phys 142:234905. CrossRefGoogle Scholar
  36. Tauer K, Gau D, Schulze S, Völkel A, Dimova R (2009) Thermal property changes of poly (N-isopropylacrylamide) microgel particles and block copolymers. Colloid Polym Sci 287:299–312. CrossRefGoogle Scholar
  37. Tsuboi Y, Nishino M, Sasaki T, Kitamura N (2005) Poly (N-Isopropylacrylamide) microparticles produced by radiation pressure of a focused laser beam: a structural analysis by confocal Raman microspectroscopy combined with a laser-trapping technique. J Phys Chem B 109(15):7033–7039. CrossRefGoogle Scholar
  38. Vosko SH, Wilk L, Nusair M (1980) Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis. Can J Phys 58(8):1200–1211. CrossRefGoogle Scholar
  39. Yah CS (2013) The toxicity of gold nanoparticles in relation to their physicochemical properties. Biomed Res 24(3):400–413. CrossRefGoogle Scholar
  40. Zuo Y, Zhao J, Gao Y, Zhang Y (2017) Controllable synthesis of P (NIPAM-co-MPTMS)/PAA–au composite materials with tunable LSPR performance. J Mater Sci 52(16):9584–9601. CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • N. Kutsevol
    • 1
  • A. Glamazda
    • 2
    Email author
  • V. Chumachenko
    • 1
  • Yu. Harahuts
    • 1
  • S. G. Stepanian
    • 2
  • A. M. Plokhotnichenko
    • 2
  • V. A. Karachevtsev
    • 2
  1. 1.Faculty of ChemistryTaras Shevchenko National University of KyivKyivUkraine
  2. 2.B.I. Verkin Institute for Low Temperature Physics and EngineeringNational Academy of Sciences of UkraineKharkivUkraine

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