Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Amphiphilic thermoresponsive copolymer bottlebrushes: synthesis, characterization, and study of their self-assembly into flower-like micelles

Abstract

Amphiphilic thermoresponsive copolymer bottlebrushes based on methoxy oligo(ethylene glycol)7 methacrylate and alkoxy(C12–C14) oligo(ethylene glycol)6 methacrylate have been successfully synthesized via RAFT and conventional free-radical polymerization in toluene. The thermoresponsive behavior of the copolymers in dilute aqueous solutions was studied by turbidimetry and laser light scattering. In water, the copolymer brushes form flower-like micelles with a hydrophobic core consisting of a polymer backbone and alkyl(C12–C14) groups and poly(ethylene glycol) linear chains and loops forming a hydrophilic shell. The size and aggregation number of the micelles and the cloud point of solutions were found to depend on the copolymer composition and chain length, as well as on the synthesis method. The conditions needed for the formation of uni- and multimolecular micelles were determined. Fluorescence techniques were used to determine the CMC of the copolymers and the drug loading capacity of the micelles using pyrene as a model hydrophobic drug.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Scheme 1
Fig. 2
Scheme 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Harmon ME, Tang M, Frank CW. A microfluidic actuator based on thermoresponsive hydrogels. Polymer. 2003;44:4547–56.

    Article  CAS  Google Scholar 

  2. Schmaljohann D. Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev. 2006;58:1655–70.

    Article  CAS  PubMed  Google Scholar 

  3. Crespy D, Rossi RM. Temperature-responsive polymers with LCST in the physiological range and their applications in textiles. Polym Int. 2007;56:1461–8.

    Article  CAS  Google Scholar 

  4. Teotia AK, Sami H, Kumar A. 1—Thermo-responsive polymers: structure and design of smart materials. In: Zhang Z, editor. Switchable and responsive surfaces and materials for biomedical applications. Oxford: Woodhead Publishing; 2015. p. 3–43.

  5. Kim Y-J, Matsunaga YT. Thermo-responsive polymers and their application as smart biomaterials. J Mater Chem B. 2017;5:4307–21.

    Article  CAS  PubMed  Google Scholar 

  6. Lutz J-F, Akdemir Ö, Hoth A. Point by point comparison of two thermosensitive polymers exhibiting a similar LCST: is the age of poly(NIPAM) over? JACS. 2006;128:13046–7.

    Article  CAS  Google Scholar 

  7. Cui Q, Wu F, Wang E. Thermosensitive behavior of poly(ethylene Glycol)-based block copolymer (PEG-b-PADMO) controlled via self-assembled microstructure. J Phys Chem B. 2011;115:5913–22.

    Article  CAS  PubMed  Google Scholar 

  8. Xu Y, Xie J, Chen L, Yuan C, Pan Y, Cheng L, et al. A novel hybrid random copolymer poly(MAPOSS-co-NIPAM-co-OEGMA-co-2VP): synthesis, characterization, self-assembly behaviors and multiple responsive properties. Macromol Res. 2013;21:1338–48.

    Article  CAS  Google Scholar 

  9. Roy D, Brooks WLA, Sumerlin BS. New directions in thermoresponsive polymers. Chem Soc Rev. 2013;42:7214–43.

    Article  CAS  PubMed  Google Scholar 

  10. Lutz J-F. Polymerization of oligo(ethylene glycol) (meth)acrylates: toward new generations of smart biocompatible materials. J Polym Sci Part A: Polym Chem. 2008;46:3459–70.

    Article  CAS  Google Scholar 

  11. Lutz J-F, Hoth A, Schade K. Design of oligo(ethylene glycol)-based thermoresponsive polymers: an optimization study. Des Monomers Polym. 2009;12:343–53.

    Article  CAS  Google Scholar 

  12. Becer CR, Hahn S, Fijten MWM, Thijs HML, Hoogenboom R, Schubert US. Libraries of methacrylic acid and oligo(ethylene glycol) methacrylate copolymers with LCST behavior. J Polym Sci Part A: Polym Chem. 2008;46:7138–47.

    Article  CAS  Google Scholar 

  13. Fournier D, Hoogenboom R, Thijs HML, Paulus RM, Schubert US. Tunable pH- and temperature-sensitive copolymer libraries by reversible addition−fragmentation chain transfer copolymerizations of methacrylates. Macromolecules. 2007;40:915–20.

    Article  CAS  Google Scholar 

  14. Hoogenboom R, Becer CR, Hahn S, Fournier DJR, Schubert US. Thermo- and pH-responsive copolymers based on oligoethyleneglycol methacrylates. Polym Prepr. 2007;48:161–2.

    CAS  Google Scholar 

  15. Liu M, Leroux J-C, Gauthier MA. Conformation–function relationships for the comb-shaped polymer pOEGMA. Prog Polym Sci. 2015;48:111–21.

    Article  Google Scholar 

  16. Zhang X, Dai Y. Recent development of brush polymers via polymerization of poly(ethylene glycol)-based macromonomers. Polym Chem. 2019;10:2212–22.

    Article  CAS  Google Scholar 

  17. Badi N. Non-linear PEG-based thermoresponsive polymer systems. Prog Polym Sci. 2017;66:54–79.

    Article  CAS  Google Scholar 

  18. Vancoillie G, Frank D, Hoogenboom R. Thermoresponsive poly(oligo ethylene glycol acrylates). Prog Polym Sci. 2014;39:1074–95.

    Article  CAS  Google Scholar 

  19. Hirai Y, Terashima T, Takenaka M, Sawamoto M. Precision self-assembly of amphiphilic random copolymers into uniform and self-sorting nanocompartments in water. Macromolecules. 2016;49:5084–91.

    Article  CAS  Google Scholar 

  20. Kimura Y, Terashima T, Sawamoto M. Macromol. Chem. Phys. 18/2017. Macromol Chem Phys. 2017;218. https://onlinelibrary.wiley.com/doi/epdf/10.1002/macp.201700230.

  21. Hattori G, Hirai Y, Sawamoto M, Terashima T. Self-assembly of PEG/dodecyl-graft amphiphilic copolymers in water: consequences of the monomer sequence and chain flexibility on uniform micelles. Polym Chem. 2017;8:7248–59.

    Article  CAS  Google Scholar 

  22. Terashima T, Sugita T, Fukae K, Sawamoto M. Synthesis and single-chain folding of amphiphilic random copolymers in water. Macromolecules. 2014;47:589–600.

    Article  CAS  Google Scholar 

  23. Terashima T, Sugita T, Sawamoto M. Single-chain crosslinked star polymers via intramolecular crosslinking of self-folding amphiphilic copolymers in water. Polym J. 2015;47:667.

    Article  CAS  Google Scholar 

  24. Koda Y, Terashima T, Sawamoto M. Multimode self-folding polymers via reversible and thermoresponsive self-assembly of amphiphilic/fluorous random copolymers. Macromolecules. 2016;49:4534–43.

    Article  CAS  Google Scholar 

  25. Matsumoto K, Terashima T, Sugita T, Takenaka M, Sawamoto M. Amphiphilic random copolymers with hydrophobic/hydrogen-bonding urea pendants: self-folding polymers in aqueous and organic media. Macromolecules. 2016;49:7917–27.

    Article  CAS  Google Scholar 

  26. Azuma Y, Terashima T, Sawamoto M. Self-folding polymer iron catalysts for living radical polymerization. ACS Macro Lett. 2017;6:830–5.

    Article  CAS  Google Scholar 

  27. Matsumoto M, Takenaka M, Sawamoto M, Terashima T. Self-assembly of amphiphilic block pendant polymers as microphase separation materials and folded flower micelles. Polym Chem. 2019;10:4954–61.

    Article  CAS  Google Scholar 

  28. Cho HY, Krys P, Szcześniak K, Schroeder H, Park S, Jurga S, et al. Synthesis of poly(OEOMA) using macromonomers via “grafting-through” ATRP. Macromolecules. 2015;48:6385–95.

    Article  CAS  Google Scholar 

  29. Bejagam KK, Singh SK, Ahn R, Deshmukh SA. Unraveling the conformations of backbone and side chains in thermosensitive bottlebrush polymers. Macromolecules. 2019;52:9398–408.

    Article  CAS  Google Scholar 

  30. Alaboalirat M, Qi L, Arrington KJ, Qian S, Keum JK, Mei H, et al. Amphiphilic bottlebrush block copolymers: analysis of aqueous self-assembly by small-angle neutron scattering and surface tension measurements. Macromolecules. 2019;52:465–76.

    Article  CAS  Google Scholar 

  31. Rathgeber S, Pakula T, Wilk A, Matyjaszewski K, Beers KL. On the shape of bottle-brush macromolecules: Systematic variation of architectural parameters. J Chem Phys. 2005;122:124904.

    Article  PubMed  Google Scholar 

  32. Li X, ShamsiJazeyi H, Pesek SL, Agrawal A, Hammouda B, Verduzco R. Thermoresponsive PNIPAAM bottlebrush polymers with tailored side-chain length and end-group structure. Soft Matter. 2014;10:2008–15.

    Article  CAS  PubMed  Google Scholar 

  33. Chatterjee D, Vilgis TA. Scaling laws of bottle-brush polymers in dilute solutions. Macromol Theory Simul. 2016;25:518–23.

    Article  CAS  Google Scholar 

  34. Dutta S, Wade MA, Walsh DJ, Guironnet D, Rogers SA, Sing CE. Dilute solution structure of bottlebrush polymers. Soft Matter. 2019;15:2928–41.

    Article  CAS  PubMed  Google Scholar 

  35. Paturej J, Sheiko SS, Panyukov S, Rubinstein M. Molecular structure of bottlebrush polymers in melts. Sci Adv. 2016;2:e1601478.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Pesek SL, Xiang Q, Hammouda B, Verduzco R. Small-angle neutron scattering analysis of bottlebrush backbone and side chain flexibility. J Polym Sci Part B: Polym Phys. 2017;55:104–11.

    Article  CAS  Google Scholar 

  37. Foster JC, Varlas S, Couturaud B, Coe Z, O’Reilly RK. Getting into shape: reflections on a new generation of cylindrical nanostructures’ self-assembly using polymer building blocks. JACS. 2019;141:2742–53.

    Article  CAS  Google Scholar 

  38. Qin S, Matyjaszewski K, Xu H, Sheiko SS. Synthesis and visualization of densely grafted molecular brushes with crystallizable poly(octadecyl methacrylate) block segments. Macromolecules. 2003;36:605–12.

    Article  CAS  Google Scholar 

  39. Verduzco R, Li X, Pesek SL, Stein GE. Structure, function, self-assembly, and applications of bottlebrush copolymers. Chem Soc Rev. 2015;44:2405–20.

    Article  CAS  PubMed  Google Scholar 

  40. Ommura Y, Imai S, Takenaka M, Ouchi M, Terashima T. Selective coupling and polymerization of folded polymer micelles to nanodomain self-assemblies. ACS Macro Lett. 2020;9:426–30.

    Article  CAS  Google Scholar 

  41. Imai S, Hirai Y, Nagao C, Sawamoto M, Terashima T. Programmed self-assembly systems of amphiphilic random copolymers into size-controlled and thermoresponsive micelles in water. Macromolecules. 2018;51:398–409.

    Article  CAS  Google Scholar 

  42. Shibata M, Matsumoto M, Hirai Y, Takenaka M, Sawamoto M, Terashima T. Intramolecular folding or intermolecular self-assembly of amphiphilic random copolymers: on-demand control by pendant design. Macromolecules. 2018;51:3738–45.

    Article  CAS  Google Scholar 

  43. Knop K, Pavlov GM, Rudolph T, Martin K, Pretzel D, Jahn BO, et al. Amphiphilic star-shaped block copolymers as unimolecular drug delivery systems: investigations using a novel fungicide. Soft Matter. 2013;9:715–26.

    Article  CAS  Google Scholar 

  44. Liu H, Farrell S, Uhrich K. Drug release characteristics of unimolecular polymeric micelles. J Control Release. 2000;68:167–74.

    Article  CAS  PubMed  Google Scholar 

  45. Fan X, Li Z, Loh XJ. Recent development of unimolecular micelles as functional materials and applications. Polym Chem. 2016;7:5898–919.

    Article  CAS  Google Scholar 

  46. Ordanini S, Cellesi F. Complex polymeric architectures self-assembling in unimolecular micelles: preparation, characterization and drug nanoencapsulation. Pharmaceutics. 2018;10:209.

  47. Fineman M, Ross SD. Linear method for determining monomer reactivity ratios in copolymerization. J Polym Sci. 1950;5:259–62.

    Article  CAS  Google Scholar 

  48. Orekhov DV, Kamorin DM, Simagin AS, Arifullin IR, Kazantsev OA, Sivokhin AP, et al. Molecular brushes based on copolymers of alkoxy oligo(ethylene glycol) methacrylates and dodecyl(meth)acrylate: features of synthesis by conventional free radical polymerization. Polym Bull. 2020. https://doi.org/10.1007/s00289-020-03390-2.

  49. Lutz J-F, Akdemir Ö, Hoth A. Point by point comparison of two thermosensitive polymers exhibiting a similar LCST: is the age of poly(NIPAM) over? J Am Chem Soc. 2006;128:13046–7.

    Article  CAS  PubMed  Google Scholar 

  50. Blackman LD, Gibson MI, O’Reilly RK. Probing the causes of thermal hysteresis using tunable Nagg micelles with linear and brush-like thermoresponsive coronas. Polym Chem. 2017;8:233–44.

    Article  CAS  PubMed  Google Scholar 

  51. Vieira NAB, Neto JR, Tiera MJ. Synthesis, characterization and solution properties of amphiphilic N-isopropylacrylamide–poly(ethylene glycol)–dodecyl methacrylate thermosensitive polymers. Colloids Surf A: Physicochemical Eng Asp. 2005;262:251–9.

    Article  CAS  Google Scholar 

  52. Fanaian S, Al-Manasir N, Zhu K, Kjøniksen A-L, Nyström B. Effects of Hofmeister anions on the flocculation behavior of temperature-responsive poly(N-isopropylacrylamide) microgels. Colloid Polym Sci. 2012;290:1609–16.

    Article  CAS  Google Scholar 

  53. Larrañeta E, Isasi JR. Phase behavior of reverse poloxamers and poloxamines in water. Langmuir. 2013;29:1045–53.

    Article  PubMed  Google Scholar 

  54. Xing XM, Liu GM, Ding YW, Zhang GZ. Revisiting the thermosensitivity of poly(acrylamide-co-diacetone acrylamide). Chin J Polym Sci (Engl Ed). 2014;32:531–9.

    Article  CAS  Google Scholar 

  55. Nunez CM, Chiou B-S, Andrady AL, Khan SA. Solution rheology of hyperbranched polyesters and their blends with linear polymers. Macromolecules. 2000;33:1720–6.

    Article  CAS  Google Scholar 

  56. Wang L, He X. Conformation of nonideal hyperbranched polymer in ABn (n = 2, 4) type polymerization. J Polym Sci, Part B: Polym Phys. 2010;48:610–6.

    Article  CAS  Google Scholar 

  57. Leong NS, Hasan M, Phillips DJ, Saaka Y, O’Reilly RK, Gibson MI. Polymers with molecular weight dependent LCSTs are essential for cooperative behaviour. Polym Chem. 2012;3:794–9.

    Article  Google Scholar 

  58. Roth PJ, Jochum FD, Forst FR, Zentel R, Theato P. Influence of end groups on the stimulus-responsive behavior of poly[oligo(ethylene glycol) methacrylate] in water. Macromolecules. 2010;43:4638–45.

    Article  CAS  Google Scholar 

  59. Ma Y, Ye C, Zhang C, Tangvijitsakul P, Soucek MD, Zacharia NS, et al. Influence of RAFT end-groups on the water swelling of poly(N-propyl methacrylate). J Polym Sci Part B: Polym Phys. 2017;55:77–84.

    Article  CAS  Google Scholar 

  60. Du J, Willcock H, Patterson JP, Portman I, O’Reilly RK. Self-assembly of hydrophilic homopolymers: a matter of RAFT end groups. Small. 2011;7:2070–80.

    Article  CAS  PubMed  Google Scholar 

  61. Willcock H, O’Reilly RK. End group removal and modification of RAFT polymers. Polym Chem. 2010;1:149–57.

    Article  CAS  Google Scholar 

  62. Wang F, Bronich TK, Kabanov AV, Rauh RD, Roovers J. Synthesis and evaluation of a star amphiphilic block copolymer from poly(ε-caprolactone) and poly(ethylene glycol) as a potential drug delivery carrier. Bioconjugate Chem. 2005;16:397–405.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was performed within the framework of the state assignment in the sphere of scientific activity (topic №FSWE-2020-0008).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexey Р. Sivokhin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sivokhin, A.Р., Orekhov, D.V., Kazantsev, O.A. et al. Amphiphilic thermoresponsive copolymer bottlebrushes: synthesis, characterization, and study of their self-assembly into flower-like micelles. Polym J 53, 655–665 (2021). https://doi.org/10.1038/s41428-020-00456-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41428-020-00456-w

This article is cited by

Search

Quick links