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:

Thermoresponsive glycopolymer vesicles: in situ observation of morphological changes and triggered cargo release

Polymer Journal volume 53, pages 1251–1258 (2021)Cite this article

Subjects

Abstract

Thermoresponsive polymer vesicles are promising drug-delivery carriers because of their ability to release cargo in a controlled manner. However, the process of thermoresponsive vesicle disassembly has attracted only limited attention to date, and the details remain elusive. Herein, we report using small-angle X-ray scattering and confocal laser scanning microscopy for in situ observation of the disassembly process during the cooling of thermoresponsive maltopentaose-b-poly(propylene oxide) polymer vesicle solutions. Notably, vesicle collapse mainly involves three discrete steps, not a concerted process. We also demonstrate that protein-loaded vesicles can be triggered to release their cargo upon cooling and that released protein retains its enzymatic activity. This study can thus provide a basis for generating guidelines for using thermoresponsive polymer vesicles in the triggered release of cargo and facilitating the development of new thermoresponsive materials based on poly(propylene oxide).

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

Similar content being viewed by others

References

  1. Discher DE, Eisenberg A. Polymer vesicles. Science. 2002;297:967. https://doi.org/10.1126/science.1074972

    Article  CAS  PubMed  Google Scholar 

  2. Antonietti M, Förster S. Vesicles and liposomes: a self-assembly principle beyond lipids. Adv Mater. 2003;15:1323–33. https://doi.org/10.1002/adma.200300010

    Article  CAS  Google Scholar 

  3. Zhu Y, Yang B, Chen S, Du J. Polymer vesicles: mechanism, preparation, application, and responsive behavior. Prog Polym Sci. 2017;64:1–22. https://doi.org/10.1016/j.progpolymsci.2015.05.001

    Article  CAS  Google Scholar 

  4. Tanner P, Baumann P, Enea R, Onaca O, Palivan C, Meier W. Polymeric vesicles: from drug carriers to nanoreactors and artificial organelles. Acc Chem Res. 2011;44:1039–49. https://doi.org/10.1021/ar200036k

    Article  CAS  PubMed  Google Scholar 

  5. Iqbal S, Blenner M, Alexander-Bryant A, Larsen J. Polymersomes for therapeutic delivery of protein and nucleic acid macromolecules: from design to therapeutic applications. Biomacromolecules. 2020;21:1327–50. https://doi.org/10.1021/acs.biomac.9b01754

    Article  CAS  PubMed  Google Scholar 

  6. Che H, van Hest JCM. Adaptive polymersome nanoreactors. ChemNanoMat. 2019;5:1092–109. https://doi.org/10.1002/cnma.201900245

    Article  CAS  Google Scholar 

  7. Nishimura T, Akiyoshi K. Biotransporting biocatalytic reactors toward therapeutic nanofactories. Adv Sci. 2018;5:1800801. https://doi.org/10.1002/advs.201800801

    Article  CAS  Google Scholar 

  8. Barenholz Y. Doxil® — The first FDA-approved nano-drug: Lessons learned. J Control Release. 2012;160:117–34. https://doi.org/10.1016/j.jconrel.2012.03.020

    Article  CAS  PubMed  Google Scholar 

  9. Boswell GW, Buell D, Bekersky I. AmBisome (Liposomal Amphotericin B): A Comparative Review. J Clin Pharmacol. 1998;38:583–92. https://doi.org/10.1002/j.1552-4604.1998.tb04464.x

    Article  CAS  PubMed  Google Scholar 

  10. Ichikawa K, Takeuchi Y, Yonezawa S, Hikita T, Kurohane K, Namba Y, Oku N. Antiangiogenic photodynamic therapy (PDT) using Visudyne causes effective suppression of tumor growth. Cancer Lett. 2004;205:39–48. https://doi.org/10.1016/j.canlet.2003.10.001

    Article  CAS  PubMed  Google Scholar 

  11. Wolfram J, Ferrari M. Clinical cancer nanomedicine. Nano Today. 2019;25:85–98. https://doi.org/10.1016/j.nantod.2019.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nishimura T, Shishi S, Sasaki Y, Akiyoshi K. Thermoresponsive polysaccharide graft polymer vesicles with tunable size and structural memory. J Am Chem Soc. 2020;142:11784–90. https://doi.org/10.1021/jacs.0c02290

    Article  CAS  PubMed  Google Scholar 

  13. Zhou Y, Yan D, Dong W, Tian Y. Temperature-responsive phase transition of polymer vesicles: real-time morphology observation and molecular mechanism. J Phys Chem B. 2007;111:1262–70. https://doi.org/10.1021/jp0673563

    Article  CAS  PubMed  Google Scholar 

  14. Qin S, Geng Y, Discher DE, Yang S. Temperature-controlled assembly and release from polymer vesicles of Poly(ethylene oxide)-block- poly(N-isopropylacrylamide). Adv Mater. 2006;18:2905–9. https://doi.org/10.1002/adma.200601019

    Article  CAS  Google Scholar 

  15. Li Y, Lokitz BS, McCormick CL. Thermally responsive vesicles and their structural “locking” through polyelectrolyte complex formation. Angew Chem Int Ed. 2006;45:5792–5. https://doi.org/10.1002/anie.200602168

    Article  CAS  Google Scholar 

  16. Cabane E, Malinova V, Menon S, Palivan CG, Meier W. Photoresponsive polymersomes as smart, triggerable nanocarriers. Soft Matter. 2011;7:9167–76. https://doi.org/10.1039/C1SM05880K

    Article  CAS  Google Scholar 

  17. Zhao P, Xia J, Cao M, Xu H. Wavelength-controlled light-responsive polymer vesicle based on Se–S dynamic chemistry. ACS Macro Lett. 2020;9:163–8. https://doi.org/10.1021/acsmacrolett.9b00983

    Article  CAS  Google Scholar 

  18. Wang X, Yao C, Zhang G, Liu S. Regulating vesicle bilayer permeability and selectivity via stimuli-triggered polymersome-to-PICsome transition. Nat Commun. 2020;11:1524. https://doi.org/10.1038/s41467-020-15304-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shi Z, Zhou Y, Yan D. Facile fabrication of pH-responsive and size-controllable polymer vesicles from a commercially available hyperbranched polyester. Macromol Rapid Commun. 2008;29:412–8. https://doi.org/10.1002/marc.200700673

    Article  CAS  Google Scholar 

  20. Yu S, Azzam T, Rouiller I, Eisenberg A. “Breathing” vesicles. J Am Chem Soc. 2009;131:10557–66. https://doi.org/10.1021/ja902869q

    Article  CAS  PubMed  Google Scholar 

  21. Yan Q, Wang J, Yin Y, Yuan J. Breathing polymersomes: CO2-tuning membrane permeability for size-selective release, separation, and reaction. Angew Chem Int Ed. 2013;52:5070–3. https://doi.org/10.1002/anie.201300397

    Article  CAS  Google Scholar 

  22. Ren T, Wu W, Jia M, Dong H, Li Y, Ou Z. Reduction-cleavable polymeric vesicles with efficient glutathione-mediated drug release behavior for reversing drug resistance. ACS Appl Mater Interfaces. 2013;5:10721–30. https://doi.org/10.1021/am402860v

    Article  CAS  PubMed  Google Scholar 

  23. Onaca O, Enea R, Hughes DW, Meier W. Stimuli-responsive polymersomes as nanocarriers for drug and gene delivery. Macromol Biosci. 2009;9:129–39. https://doi.org/10.1002/mabi.200800248

    Article  CAS  PubMed  Google Scholar 

  24. Li M-H, Keller P. Stimuli-responsive polymer vesicles. Soft Matter. 2009;5:927–37. https://doi.org/10.1039/B815725A

    Article  CAS  Google Scholar 

  25. Feng A, Yuan J. Smart nanocontainers: progress on novel stimuli-responsive polymer vesicles. Macromol Rapid Commun. 2014;35:767–79. https://doi.org/10.1002/marc.201300866

    Article  CAS  PubMed  Google Scholar 

  26. Bordat A, Boissenot T, Nicolas J, Tsapis N. Thermoresponsive polymer nanocarriers for biomedical applications. Adv Drug Deliv Rev. 2019;138:167–92. https://doi.org/10.1016/j.addr.2018.10.005

    Article  CAS  PubMed  Google Scholar 

  27. Roy D, Brooks WLA, Sumerlin BS. New directions in thermoresponsive polymers. Chem Soc Rev. 2013;42:7214–43. https://doi.org/10.1039/C3CS35499G

    Article  CAS  PubMed  Google Scholar 

  28. Nishimura T, Sasaki Y, Akiyoshi K. Biotransporting self-assembled nanofactories using polymer vesicles with molecular permeability for enzyme prodrug cancer therapy. Adv Mater. 2017;29:1702406. https://doi.org/10.1002/adma.201702406

    Article  CAS  Google Scholar 

  29. Nishimura T, de Campo L, Iwase H, Akiyoshi K. Determining the hydration in the hydrophobic layer of permeable polymer vesicles by neutron scattering. Macromolecules. 2020;53:7546–51. https://doi.org/10.1021/acs.macromol.0c01261

    Article  CAS  Google Scholar 

  30. Weiss TM, Narayanan T, Gradzielski M. Dynamics of spontaneous vesicle formation in fluorocarbon and hydrocarbon surfactant mixtures. Langmuir. 2008;24:3759–66. https://doi.org/10.1021/la703515j

    Article  CAS  PubMed  Google Scholar 

  31. Weiss TM, Narayanan T, Wolf C, Gradzielski M, Panine P, Finet S, Helsby WI. Dynamics of the self-assembly of unilamellar vesicles. Phys Rev Lett. 2005;94:038303. https://doi.org/10.1103/PhysRevLett.94.038303

    Article  CAS  PubMed  Google Scholar 

  32. Fuhrmans M, Müller M. Mechanisms of vesicle spreading on surfaces: coarse-grained simulations. Langmuir. 2013;29:4335–49. https://doi.org/10.1021/la400119e

    Article  CAS  PubMed  Google Scholar 

  33. Nguyen XD, Park DH, Paik H-j, Jeon HJ, Huh J, Go JS. Microfluidic tracking of the growth of polymeric vesicles in hydrodynamic flow. ACS Appl Polym Mater. 2020;2:5845–50. https://doi.org/10.1021/acsapm.0c01089

    Article  CAS  Google Scholar 

  34. Yamada NL. Kinetic process of formation and reconstruction of small unilamellar vesicles consisting of long- and short-chain lipids. Langmuir. 2012;28:17381–8. https://doi.org/10.1021/la3026842

    Article  CAS  PubMed  Google Scholar 

  35. Battaglia G, Ryan AJ. Pathways of polymeric vesicle formation. J Phys Chem B. 2006;110:10272–9. https://doi.org/10.1021/jp060728n

    Article  CAS  PubMed  Google Scholar 

  36. Mable CJ, Derry MJ, Thompson KL, Fielding LA, Mykhaylyk OO, Armes SP. Time-resolved SAXS studies of the kinetics of thermally triggered release of encapsulated silica nanoparticles from block copolymer vesicles. Macromolecules. 2017;50:4465–73. https://doi.org/10.1021/acs.macromol.7b00475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the JSPS in the form of Grants-in-Aid for Scientific Research (S: 16H06313; B: 18H01845), the Asahi Glass Foundation, and the MEXT Leading Initiative for Excellent Young Researchers. SAXS experiments were conducted at the BL40B2 beamline of SPring-8 under proposal numbers 2017A1241 and 2020A1070.

Author information

Authors and Affiliations

  1. Department of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu University, Nagano, Japan

    Tomoki Nishimura

  2. Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan

    Yoshihiro Sasaki

Authors
  1. Tomoki Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshihiro Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazunari Akiyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the writing of this manuscript. All authors have given approval to the final version of the manuscript.

Corresponding author

Correspondence to Tomoki Nishimura.

Ethics declarations

Conflict of interest

The authors declare no competing 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

Nishimura, T., Sasaki, Y. & Akiyoshi, K. Thermoresponsive glycopolymer vesicles: in situ observation of morphological changes and triggered cargo release. Polym J 53, 1251–1258 (2021). https://doi.org/10.1038/s41428-021-00488-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41428-021-00488-w

Search

Advanced search

Quick links