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.

  • Focus Review
  • Published:

Poly(N-isopropylacrylamide)-based temperature- and pH-responsive polymer materials for application in biomedical fields

Polymer Journal volume 54, pages 1419–1430 (2022)Cite this article

Subjects

Abstract

The synthesis and application of stimuli-responsive polymer materials have been extensively studied. Among stimuli-responsive polymers, thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) is the most widely investigated. PNIPAAm-based polymers undergo a reversible hydrophilic/hydrophobic phase transition in response to temperature. In addition, by introducing sites that are responsive to physical and chemical stimuli into PNIPAAm-based polymers, they also undergo phase transitions in response to stimuli, such as light, pH, oxidation/reduction, and enzyme activity. In this focus review, recent advancements in the applications of stimuli-responsive polymers based on PNIPAAm in biomedical fields are summarized, with an emphasis on our own research. In particular, a summary of the design of polymers for application in the separation and purification of (bio)pharmaceutical products and controlled cellular uptake is provided. First, temperature-responsive chromatography with PNIPAAm-modified silica beads is introduced. Thereafter, temperature- and pH-responsive polymers based on PNIPAAm used in imaging and drug delivery applications are discussed. Finally, the conclusions are presented, and future perspectives for the biomedical applications of stimuli-responsive polymers are discussed.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Stuart MAC, Huck WTS, Genzer J, Müller M, Ober C, Stamm M, et al. Emerging applications of stimuli-responsive polymer materials. Nat Mater. 2010;9:101–13.

    Article  PubMed  Google Scholar 

  2. Jochum FD, Theato P. Temperature- and light-responsive smart polymer materials. Chem Soc Rev. 2013;42:7468–83.

    Article  CAS  PubMed  Google Scholar 

  3. Ulijn RV. Enzyme-responsive materials: a new class of smart biomaterials. J Mater Chem. 2006;16:2217–25.

    Article  CAS  Google Scholar 

  4. Meng F, Hennink WE, Zhong Z. Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials. 2009;30:2180–98.

    Article  CAS  PubMed  Google Scholar 

  5. Hasuike E, Akimoto AM, Kuroda R, Matsukawa K, Hiruta Y, Kanazawa H, et al. Reversible conformational changes in the parallel type G-quadruplex structure inside a thermoresponsive hydrogel. Chem Commun. 2017;53:3142–4.

    Article  CAS  Google Scholar 

  6. Kim YS, Tamate R, Akimoto AM, Yoshida R. Recent developments in self-oscillating polymeric systems as smart materials: from polymers to bulk hydrogels. Mater Horiz. 2017;4:38–54.

    Article  CAS  Google Scholar 

  7. Tanaka T. Collapse of gels and the critical endpoint. Phys Rev Lett. 1978;40:820–3.

    Article  CAS  Google Scholar 

  8. Osada Y, Gong J. Stimuli-responsive polymer gels and their application to chemomechanical systems. Prog Polym Sci. 1993;18:187–226.

    Article  CAS  Google Scholar 

  9. Schild HG. Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci. 1992;17:163–249.

    Article  CAS  Google Scholar 

  10. Heskins M, Guillet JE. Solution properties of poly(N-isopropylacrylamide). J Macromol Sci Chem. 1968;2:1441–55.

    Article  CAS  Google Scholar 

  11. Podewitz M, Wang Y, Quoika PK, Loeffler JR, Schauperl M, Liedl KR. Coil–globule transition thermodynamics of poly(N-isopropylacrylamide). J Phys Chem B. 2019;123:8838–47.

    Article  CAS  PubMed  Google Scholar 

  12. Wu C, Wang X. Globule-to-coil transition of a single homopolymer chain in solution. Phys Rev Lett. 1998;80:4092–4.

    Article  CAS  Google Scholar 

  13. Zhang Y, Furyk S, Bergbreiter DE, Cremer PS. Specific ion effects on the water solubility of macromolecules: PNIPAM and the Hofmeister series. J Am Chem Soc. 2005;127:14505–10.

    Article  CAS  PubMed  Google Scholar 

  14. Hiruta Y, Nagumo Y, Suzuki Y, Funatsu T, Ishikawa Y, Kanazawa H. The effects of anionic electrolytes and human serum albumin on the LCST of poly(N-isopropylacrylamide)-based temperature-responsive copolymers. Colloids Surf B. 2015;132:299–304.

    Article  CAS  Google Scholar 

  15. Hiruta Y, Shimamura M, Matsuura M, Maekawa Y, Funatsu T, Suzuki Y, et al. Temperature-responsive fluorescence polymer probes with accurate thermally controlled cellular uptakes. ACS Macro Lett. 2014;3:281–5.

    Article  CAS  PubMed  Google Scholar 

  16. Feil H, Bae YH, Feijen J, Kim SW. Effect of comonomer hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers. Macromolecules. 1993;26:2496–500.

    Article  CAS  Google Scholar 

  17. Li J, Kaku T, Tokura Y, Matsukawa K, Homma K, Nishimoto T, et al. Adsorption–desorption control of fibronectin in real time at the liquid/polymer interface on a quartz crystal microbalance by thermoresponsivity. Biomacromolecules. 2019;20:1748–55.

    Article  CAS  PubMed  Google Scholar 

  18. Yin X, Hoffman AS, Stayton PS. Poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH. Biomacromolecules. 2006;7:1381–5.

    Article  CAS  PubMed  Google Scholar 

  19. Okubo M, Ahmad H, Suzuki T. Synthesis of temperature-sensitive micron-sized monodispersed composite polymer particles and its application as a carrier for biomolecules. Colloid Polym Sci. 1998;276:470–5.

    Article  CAS  Google Scholar 

  20. Matyjaszewski K, Spanswick J. Controlled/living radical polymerization. Mater Today. 2005;8:26–33.

    Article  CAS  Google Scholar 

  21. Žuvela P, Skoczylas M, Jay Liu J, Ba̧czek T, Kaliszan R, Wong MW, et al. Column characterization and selection systems in reversed-phase high-performance liquid chromatography. Chem Rev. 2019;119:3674–729.

    Article  PubMed  Google Scholar 

  22. Mochida M, Nagai Y, Kumagai H, Imai H, Citterio D, Hiruta Y. A biomimetic hybrid material consisting of CaCO3 mesoporous microspheres and an alternating copolymer for reversed-phase HPLC. J. Mater Chem B. 2019;7:4771–7.

    Article  CAS  Google Scholar 

  23. Zhang Z, Zheng Y, Chen J, Zhang Q, Ni Y, Liang X. Facile synthesis of monodisperse magnesium oxide microspheres via seed-induced precipitation and their applications in high- performance liquid chromatography. Adv Funct Mater. 2007;17:2447–54.

    Article  CAS  Google Scholar 

  24. Nagase K, Kanazawa H. Temperature-responsive chromatography for bioseparations: a review. Anal Chim Acta. 2020;1138:191–212.

    Article  CAS  PubMed  Google Scholar 

  25. Sakata K, Ohkubo K, Hiruta Y, Ayano E, Kanazawa H. Temperature-responsive chromatography using a functional polymer modified stationary phase with molecular recognition sites. Kobunshi Ronbunshu. 2014;71:293–301.

    Article  CAS  Google Scholar 

  26. Kanazawa H, Yamamoto K, Matsushima Y, Takai N, Kikuchi A, Sakurai Y, et al. Temperature-responsive chromatography using poly(N-isopropylacrylamide)-modified silica. Anal Chem. 1996;68:100–5.

    Article  CAS  PubMed  Google Scholar 

  27. Mikuma T, Kuroki T, Yoshikawa M, Uchida R, Hiruta Y, Kanazawa H. Analysis of psychoactive drugs by temperature-responsive chromatography. Chromatography. 2017;38:115–21.

    Article  CAS  Google Scholar 

  28. Maekawa Y, Okamoto N, Okada Y, Nagase K, Kanazawa H. Green analytical method for the simultaneous analysis of cytochrome P450 probe substrates by poly(N-isopropylacrylamide)-based temperature-responsive chromatography. Sci Rep. 2020;10:8828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kanazawa H, Nishikawa M, Mizutani A, Sakamoto C, Morita-Murase Y, Nagata Y, et al. Aqueous chromatographic system for separation of biomolecules using thermoresponsive polymer modified stationary phase. J Chromatogr A. 2008;1191:157–61.

    Article  CAS  PubMed  Google Scholar 

  30. Okubo K, Ikeda K, Oaku A, Hiruta Y, Nagase K, Kanazawa H. Protein purification using solid-phase extraction on temperature-responsive hydrogel-modified silica beads. J Chromatogr A. 2018;1568:38–48.

    Article  CAS  PubMed  Google Scholar 

  31. Nomoto D, Nagase K, Nakamura Y, Kanazawa H, Citterio D, Hiruta Y. Anion species-triggered antibody separation system utilizing a thermo-responsive polymer column under optimized constant temperature. Colloids Surf B. 2021;205:111890.

    Article  CAS  Google Scholar 

  32. Nagase K, Inanaga D, Ichikawa D, Mizutani Akimoto A, Hattori Y, Kanazawa H. Temperature-modulated cell-separation column using temperature-responsive cationic copolymer hydrogel-modified silica beads. Colloids Surf B. 2019;178:253–62.

    Article  CAS  Google Scholar 

  33. Nagase K, Uchikawa N, Hirotani T, Akimoto AM, Kanazawa H. Thermoresponsive anionic copolymer brush-grafted surfaces for cell separation. Colloids Surf B. 2020;185:110565.

    Article  CAS  Google Scholar 

  34. Konishi T, Mizutani Akimoto A, Nishimoto T, Tokura Y, Tenjimbayashi M, Homma K, et al. Crosslinked poly(N-Isopropylacrylamide)-based microfibers as cell manipulation materials with prompt cell detachment. Macromol Rapid Commun. 2019;40:1900464.

    Article  CAS  Google Scholar 

  35. Yakushiji T, Sakai K, Kikuchi A, Aoyagi T, Sakurai Y, Okano T. Effects of cross-linked structure on temperature-responsive hydrophobic interaction of poly(N-isopropylacrylamide) hydrogel-modified surfaces with steroids. Anal Chem. 1999;71:1125–30.

    Article  CAS  Google Scholar 

  36. Nagase K, Kobayashi J, Kikuchi A, Akiyama Y, Kanazawa H, Okano T. Interfacial property modulation of thermoresponsive polymer brush surfaces and their interaction with biomolecules. Langmuir. 2007;23:9409–15.

    Article  CAS  PubMed  Google Scholar 

  37. Kanazawa H, Kashiwase Y, Yamamoto K, Matsushima Y, Kikuchi A, Sakurai Y, et al. Temperature-responsive liquid chromatography. 2. Effects of hydrophobic groups in N-isopropylacrylamide copolymer-modified silica. Anal Chem. 1997;69:823–30.

    Article  CAS  PubMed  Google Scholar 

  38. Kanazawa H, Sunamoto T, Matsushima Y, Kikuchi A, Okano T. Temperature-responsive chromatographic separation of amino acid phenylthiohydantoins using aqueous media as the mobile phase. Anal Chem. 2000;72:5961–6.

    Article  CAS  PubMed  Google Scholar 

  39. Mori H, Sutoh K, Endo T. Controlled radical polymerization of an acrylamide containing l-phenylalanine moiety via RAFT. Macromolecules. 2005;38:9055–65.

    Article  CAS  Google Scholar 

  40. Casolaro M, Cini R, Del Bello B, Ferrali M, Maellaro E. Cisplatin/hydrogel complex in cancer therapy. Biomacromolecules. 2009;10:944–9.

    Article  CAS  PubMed  Google Scholar 

  41. Feng X, Zhang Q, Liang X, Li J, Zhao Y, Chen L. Preparation, characterization and application of a chiral thermo-sensitive membrane for phenylalanine separation of the racemic mixture. J Polym Res. 2014;21:1–9.

    Article  Google Scholar 

  42. Kanazawa H, Ayano E, Sakamoto C, Yoda R, Kikuchi A, Okano T. Temperature-responsive stationary phase utilizing a polymer of proline derivative for hydrophobic interaction chromatography using an aqueous mobile phase. J Chromatogr A. 2006;1106:152–8.

    Article  CAS  PubMed  Google Scholar 

  43. Hiruta Y, Kanazashi R, Ayano E, Okano T, Kanazawa H. Temperature-responsive molecular recognition chromatography using phenylalanine and tryptophan derived polymer modified silica beads. Analyst. 2016;141:910–7.

    Article  CAS  PubMed  Google Scholar 

  44. Hiruta Y, Nagumo Y, Miki A, Okano T, Kanazawa H. Effects of terminal group and chain length on temperature-responsive chromatography utilizing poly(N-isopropylacrylamide) synthesized via RAFT polymerization. RSC Adv. 2015;5:73217–24.

    Article  CAS  Google Scholar 

  45. Mikuma T, Uchida R, Kajiya M, Hiruta Y, Kanazawa H. The use of a temperature-responsive column for the direct analysis of drugs in serum by two-dimensional heart-cutting liquid chromatography. Anal Bioanal Chem. 2017;409:1059–65.

    Article  CAS  PubMed  Google Scholar 

  46. Akimaru M, Okubo K, Hiruta Y, Kanazawa H. Temperature-responsive solid-phase extraction column for biological sample pretreatment. Anal Sci. 2015;31:881–6.

    Article  CAS  PubMed  Google Scholar 

  47. Nagase K, Ishii S, Ikeda K, Yamada S, Ichikawa D, Akimoto AM, et al. Antibody drug separation using thermoresponsive anionic polymer brush modified beads with optimised electrostatic and hydrophobic interactions. Sci Rep. 2020;10:11896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Karnebogen M, Singer D, Kallerhoff M, Ringert RH. Microcalorimetric investigations on isolated tumorous and non-tumorous tissue samples. Thermochim Acta. 1993;229:147–55.

    Article  Google Scholar 

  49. Monti M, Brandt L, Ikomi-Kumm J, Olsson H. Microcalorimetric investigation of cell metabolism in tumour cells from patients with non-Hodgkin lymphoma (NHL). Scand J Haematol. 1986;36:353–7.

    Article  CAS  PubMed  Google Scholar 

  50. Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, et al. Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002;3:487–97.

    Article  CAS  PubMed  Google Scholar 

  51. Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 2011;11:671–7.

    Article  CAS  PubMed  Google Scholar 

  52. Yuba E. Development of functional liposomes by modification of stimuli-responsive materials and their biomedical applications. J Mater Chem B. 2020;8:1093–107.

    Article  CAS  PubMed  Google Scholar 

  53. Bordat A, Boissenot T, Nicolas J, Tsapis N. Thermoresponsive polymer nanocarriers for biomedical applications. Adv Drug Deliv Rev. 2019;138:167–92.

    Article  CAS  PubMed  Google Scholar 

  54. Akimoto J, Nakayama M, Okano T. Temperature-responsive polymeric micelles for optimizing drug targeting to solid tumors. J Control Release. 2014;193:2–8.

    Article  CAS  PubMed  Google Scholar 

  55. Kono K, Hayashi H, Takagishi T. Temperature-sensitive liposomes: liposomes bearing poly (N-isopropylacrylamide). J Control Release. 1994;30:69–75.

    Article  CAS  Google Scholar 

  56. Cammas S, Suzuki K, Sone C, Sakurai Y, Kataoka K, Okano T. Thermo-responsive polymer nanoparticles with a core-shell micelle structure as site-specific drug carriers. J Control Release. 1997;48:157–64.

    Article  CAS  Google Scholar 

  57. Chung JE, Yokoyama M, Yamato M, Aoyagi T, Sakurai Y, Okano T. Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate). J Control Release. 1999;62:115–27.

    Article  CAS  PubMed  Google Scholar 

  58. Kono K, Henmi A, Yamashita H, Hayashi H, Takagishi T. Improvement of temperature-sensitivity of poly(N-isopropylacrylamide)-modified liposomes. J Control Release. 1999;59:63–75.

    Article  CAS  PubMed  Google Scholar 

  59. Kono K, Nakai R, Morimoto K, Takagishi T. Temperature-dependent interaction of thermo-sensitive polymer-modified liposomes with CV1 cells. FEBS Lett. 1999;456:306–10.

    Article  CAS  PubMed  Google Scholar 

  60. Akimoto J, Nakayama M, Sakai K, Okano T. Temperature-induced intracellular uptake of thermoresponsive polymeric micelles. Biomacromolecules. 2009;10:1331–6.

    Article  CAS  PubMed  Google Scholar 

  61. Akimoto J, Nakayama M, Sakai K, Okano T. Thermally controlled intracellular uptake system of polymeric micelles possessing poly(N-isopropylacrylamide)-based outer coronas. Mol Pharmaceutics. 2010;7:926–35.

    Article  CAS  Google Scholar 

  62. Hamai C, Yang T, Kataoka S, Cremer PS, Musser SM. Effect of average phospholipid curvature on supported bilayer formation on glass by vesicle fusion. Biophys J. 2006;90:1241–8.

    Article  CAS  PubMed  Google Scholar 

  63. Yamada A, Hiruta Y, Wang J, Ayano E, Kanazawa H. Design of environmentally responsive fluorescent polymer probes for cellular imaging. Biomacromolecules. 2015;16:2356–62.

    Article  CAS  PubMed  Google Scholar 

  64. Kanai Y, Segawa H, Miyamoto K-I, Uchino H, Takeda E, Endou H. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998;273:23629–32.

    Article  CAS  PubMed  Google Scholar 

  65. Matsuura M, Ohshima M, Hiruta Y, Nishimura T, Nagase K, Kanazawa H. LAT1-targeting thermoresponsive fluorescent polymer probes for cancer cell imaging. Int J Mol Sci. 2018;19:1646.

    Article  PubMed Central  Google Scholar 

  66. Ju XJ, Liu L, Xie R, Niu CH, Chu LY. Dual thermo-responsive and ion-recognizable monodisperse microspheres. Polymer. 2009;50:922–9.

    Article  CAS  Google Scholar 

  67. Jochum FD, Zur Borg L, Roth PJ, Theato P. Thermo- and light-responsive polymers containing photoswitchable azobenzene end groups. Macromolecules. 2009;42:7854–62.

    Article  CAS  Google Scholar 

  68. Hiruta Y, Funatsu T, Matsuura M, Wang J, Ayano E, Kanazawa H. pH/temperature-responsive fluorescence polymer probe with pH-controlled cellular uptake. Sens Actuators B Chem. 2015;207:724–31.

    Article  CAS  Google Scholar 

  69. Kolate A, Baradia D, Patil S, Vhora I, Kore G, Misra A. PEG—a versatile conjugating ligand for drugs and drug delivery systems. J Control Release. 2014;192:67–81.

    Article  CAS  PubMed  Google Scholar 

  70. Hatakeyama H, Akita H, Harashima H. A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Adv Drug Deliv Rev. 2011;63:152–60.

    Article  CAS  PubMed  Google Scholar 

  71. Wang M, Thanou M. Targeting nanoparticles to cancer. Pharmacol Res. 2010;62:90–9.

    Article  CAS  PubMed  Google Scholar 

  72. Meyer DE, Shin BC, Kong GA, Dewhirst MW, Chilkoti A. Drug targeting using thermally responsive polymers and local hyperthermia. J Control Release. 2001;74:213–24.

    Article  CAS  PubMed  Google Scholar 

  73. Hiruta Y, Nemoto R, Kanazawa H. Design and synthesis of temperature-responsive polymer/silica hybrid nanoparticles and application to thermally controlled cellular uptake. Colloids Surf B. 2017;153:2–9.

    Article  CAS  Google Scholar 

  74. Hiruta Y, Kanda Y, Katsuyama N, Kanazawa H. Dual temperature- and pH-responsive polymeric micelle for selective and efficient two-step doxorubicin delivery. RSC Adv. 2017;7:29540–9.

    Article  CAS  Google Scholar 

  75. Nemoto R, Fujieda K, Hiruta Y, Hishida M, Ayano E, Maitani Y, et al. Liposomes with temperature-responsive reversible surface properties. Colloids Surf B. 2019;176:309–16.

    Article  CAS  Google Scholar 

  76. Wang J, Ayano E, Maitani Y, Kanazawa H. Tunable surface properties of temperature-responsive polymer-modified liposomes induce faster cellular uptake. ACS Omega. 2017;2:316–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wang J, Ayano E, Maitani Y, Kanazawa H. Enhanced cellular uptake and gene silencing activity of siRNA using temperature-responsive polymer-modified liposome. Int J Pharm. 2017;523:217–28.

    Article  CAS  PubMed  Google Scholar 

  78. Maekawa-Matsuura M, Fujieda K, Maekawa Y, Nishimura T, Nagase K, Kanazawa H. LAT1-targeting thermoresponsive liposomes for effective cellular uptake by cancer cells. ACS Omega. 2019;4:6443–51.

    Article  CAS  Google Scholar 

  79. 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 

  80. Hao J, Servello J, Sista P, Biewer MC, Stefan MC. Temperature-sensitive aliphatic polyesters: synthesis and characterization of γ-substituted caprolactone monomers and polymers. J Mater Chem. 2011;21:10623–8.

    Article  CAS  Google Scholar 

  81. Weber C, Hoogenboom R, Schubert US. Temperature responsive bio-compatible polymers based on poly(ethylene oxide) and poly(2-oxazoline)s. Prog Polym Sci. 2012;37:686–714.

    Article  CAS  Google Scholar 

  82. Deng H, Liu J, Zhao X, Zhang Y, Liu J, Xu S, et al. PEG-b-PCL copolymer micelles with the ability of pH-controlled negative-to-positive charge reversal for intracellular delivery of doxorubicin. Biomacromolecules. 2014;15:4281–92.

    Article  CAS  PubMed  Google Scholar 

  83. Sano K, Kanada Y, Takahashi K, Ding N, Kanazaki K, Mukai T, et al. Enhanced delivery of radiolabeled polyoxazoline into tumors via self-aggregation under hyperthermic conditions. Mol Pharmaceutics. 2018;15:3997–4003.

    Article  CAS  Google Scholar 

  84. Cheng Y, Hao J, Lee LA, Biewer MC, Wang Q, Stefan MC. Thermally controlled release of anticancer drug from self-assembled gamma-substituted amphiphilic poly(epsilon-caprolactone) micellar nanoparticles. Biomacromolecules. 2012;13:2163–73.

    Article  CAS  PubMed  Google Scholar 

  85. Sano K, Umemoto K, Miura H, Ohno S, Iwata K, Kawakami R, et al. Feasibility of using poly[oligo(ethylene glycol) methyl ether methacrylate] as tumor-targeted carriers of diagnostic drugs. ACS Appl Polym Mater. 2022;4:4734–40.

    Article  Google Scholar 

Download references

Acknowledgements

This study was partly supported by a Grant-in-Aid for Scientific Research for Research Activity-Career Scientists (Grant No. 19K16339), Grant-in-Aid for Scientific Research (C) (Grant No. 21K06495) from the Japan Society for the Promotion of Science (JSPS), and by the Program for the Advancement of Next Generation Research Projects (Type C) at Keio. I would like to thank Editage (www.editage.jp) for their English language editing services.

Author information

Authors and Affiliations

  1. Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan

    Yuki Hiruta

Authors
  1. Yuki Hiruta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuki Hiruta.

Ethics declarations

Conflict of interest

The author declares no competing interests.

Additional information

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

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hiruta, Y. Poly(N-isopropylacrylamide)-based temperature- and pH-responsive polymer materials for application in biomedical fields. Polym J 54, 1419–1430 (2022). https://doi.org/10.1038/s41428-022-00687-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41428-022-00687-z

This article is cited by

Search

Advanced search

Quick links