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
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Harmon ME, Tang M, Frank CW. A microfluidic actuator based on thermoresponsive hydrogels. Polymer. 2003;44:4547–56.
Schmaljohann D. Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev. 2006;58:1655–70.
Crespy D, Rossi RM. Temperature-responsive polymers with LCST in the physiological range and their applications in textiles. Polym Int. 2007;56:1461–8.
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.
Kim Y-J, Matsunaga YT. Thermo-responsive polymers and their application as smart biomaterials. J Mater Chem B. 2017;5:4307–21.
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.
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.
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.
Roy D, Brooks WLA, Sumerlin BS. New directions in thermoresponsive polymers. Chem Soc Rev. 2013;42:7214–43.
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.
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.
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.
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.
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.
Liu M, Leroux J-C, Gauthier MA. Conformation–function relationships for the comb-shaped polymer pOEGMA. Prog Polym Sci. 2015;48:111–21.
Zhang X, Dai Y. Recent development of brush polymers via polymerization of poly(ethylene glycol)-based macromonomers. Polym Chem. 2019;10:2212–22.
Badi N. Non-linear PEG-based thermoresponsive polymer systems. Prog Polym Sci. 2017;66:54–79.
Vancoillie G, Frank D, Hoogenboom R. Thermoresponsive poly(oligo ethylene glycol acrylates). Prog Polym Sci. 2014;39:1074–95.
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.
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.
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.
Terashima T, Sugita T, Fukae K, Sawamoto M. Synthesis and single-chain folding of amphiphilic random copolymers in water. Macromolecules. 2014;47:589–600.
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.
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.
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.
Azuma Y, Terashima T, Sawamoto M. Self-folding polymer iron catalysts for living radical polymerization. ACS Macro Lett. 2017;6:830–5.
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.
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.
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.
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.
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.
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.
Chatterjee D, Vilgis TA. Scaling laws of bottle-brush polymers in dilute solutions. Macromol Theory Simul. 2016;25:518–23.
Dutta S, Wade MA, Walsh DJ, Guironnet D, Rogers SA, Sing CE. Dilute solution structure of bottlebrush polymers. Soft Matter. 2019;15:2928–41.
Paturej J, Sheiko SS, Panyukov S, Rubinstein M. Molecular structure of bottlebrush polymers in melts. Sci Adv. 2016;2:e1601478.
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.
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.
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.
Verduzco R, Li X, Pesek SL, Stein GE. Structure, function, self-assembly, and applications of bottlebrush copolymers. Chem Soc Rev. 2015;44:2405–20.
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.
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.
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.
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.
Liu H, Farrell S, Uhrich K. Drug release characteristics of unimolecular polymeric micelles. J Control Release. 2000;68:167–74.
Fan X, Li Z, Loh XJ. Recent development of unimolecular micelles as functional materials and applications. Polym Chem. 2016;7:5898–919.
Ordanini S, Cellesi F. Complex polymeric architectures self-assembling in unimolecular micelles: preparation, characterization and drug nanoencapsulation. Pharmaceutics. 2018;10:209.
Fineman M, Ross SD. Linear method for determining monomer reactivity ratios in copolymerization. J Polym Sci. 1950;5:259–62.
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.
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.
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.
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.
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.
Larrañeta E, Isasi JR. Phase behavior of reverse poloxamers and poloxamines in water. Langmuir. 2013;29:1045–53.
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.
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.
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.
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.
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.
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.
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.
Willcock H, O’Reilly RK. End group removal and modification of RAFT polymers. Polym Chem. 2010;1:149–57.
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.
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
Corresponding author
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
About this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41428-020-00456-w