Vesicles formed in water by synthetic macro-amphiphiles have attracted much attention as nanocontainers having properties that extend the physical and chemical limits of liposomes. We sought to develop ABA block copolymeric amphiphiles that self-assemble into unilamellar vesicles that can be further oxidatively destabilized. We selected poly(ethylene glycol) (PEG) as the hydrophilic A blocks, owing to its resistance to protein adsorption and low toxicity. As hydrophobic B blocks, we selected poly(propylene sulphide) (PPS), owing to its extreme hydrophobicity, its low glass-transition temperature, and most importantly its oxidative conversion from a hydrophobe to a hydrophile, poly(propylene sulphoxide) and ultimately poly(propylene sulphone). This is the first example of the use of oxidative conversions to destabilize such carriers. This new class of oxidation-responsive polymeric vesicles may find applications as nanocontainers in drug delivery, biosensing and biodetection.
Subscribe to Journal
Get full journal access for 1 year
only $16.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Discher, B.M. et al. Polymersomes: Tough vesicles from diblock copolymers. Science 284, 1143–1146 (1999).
Nardin, C., Hirt, T., Leukel, J. & Meier, W. Polymerized ABA triblock copolymer vesicles. Langmuir 16, 1035–1041 (2000).
Discher, D.E. & Eisenberg, A. Polymer vesicles. Science 297, 967–973 (2002).
Sommerdijk, N.A.J.M., Holder, S.J., Hiorns, R.C., Jones, R.G. & Nolte, R.J.M. Self-assembled structures from an amphiphilic multiblock copolymer containing rigid semiconductor segments. Macromolecules 33, 8289–8294 (2000).
Cornelissen, J.J.L.M., Fischer, M., Sommerdijk, N.A.J.M. & Nolte, R.J.M. Helical superstructures from charged poly(styrene)-poly(isocyanodipeptide) block copolymers. Science 280, 1427–1430 (1998).
Bermudez, H., Brannan, A.K., Hammer, D.A., Bates, F.S. & Discher, D.E. Molecular weight dependence of polymersome membrane structure, elasticity, and stability. Macromolecules 35, 8203–8208 (2002).
Aranda-Espinoza, H., Bermudez, H., Bates, F.S. & Discher, D.E. Electromechanical limits of polymersomes. Phys. Rev. Lett. 8720, 208301 (2001).
Dimova, R., Seifert, U., Pouligny, B., Förster, S. & Döbereiner, H.G. Hyperviscous diblock copolymer vesicles. Eur. Phys. J. 7, 241–250 (2002).
Lee, J.C.M. et al. Preparation, stability, and in vitro performance of vesicles made with diblock copolymers. Biotechnol. Bioeng. 73, 135–145 (2001).
Förster, S. et al. Lyotropic phase morphologies of amphiphilic block copolymers. Macromolecules 34, 4610–4623 (2001).
Hajduk, D.A., Kossuth, M.B., Hillmyer, M.A. & Bates, F.S. Complex phase behavior in aqueous solutions of poly(ethylene oxide)-poly(ethylethylene) block copolymers. J. Phys. Chem. B 102, 4269–4276 (1998).
Lasic, D.D. & Needham, D. The “Stealth” Liposome: A Prototypical Biomaterial. Chem. Rev. 95, 2601–2628 (1995).
Allen, T.M., Sapra, P., Moase, E., Moreira, J. & Iden, D. Adventures in targeting. J Lipos. Res. 12, 5–12 (2002).
Torchilin, V.P., Rammohan, R., Weissig, V. & Levchenko, T.S. Tat peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc. Natl Acad. Sci. USA 98, 8786–8791 (2001).
Halliwell, B., Clement, M.V. & Long, L.H. Hydrogen peroxide in the human body. FEBS Lett. 486, 10–13 (2000).
Ohshima, H., Tatemichi, M. & Sawa, T. Chemical basis of inflammation-induced carcinogenesis*1. Arch. Biochem. Biophys. 417, 3–11 (2003).
Napoli, A., Tirelli, N., Kilcher, G. & Hubbell, J.A. New synthetic methodologies for amphiphilic multiblock copolymers of ethylene glycol and propylene sulfide. Macromolecules 34, 8913–8917 (2001).
Schillen, K., Bryskhe, K. & Mel'nikova, Y. Vesicles Formed from a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer in dilute aqueous solution. Macromolecules 32, 6885–6888 (1999).
Nicol, E., Nicolai, T. & Durand, D. Dynamics of poly(propylene sulfide) studied by dynamic mechanical measurments and dielectric spectroscopy. Macromolecules 32, 7530–7536 (1999).
Napoli, A., Tirelli, N., Wehrli, E. & Hubbell, J.A. Lyotropic behavior in water of amphiphilic aba triblock copolymers based on poly(propylene sulfide) and poly(ethylene glycol). Langmuir 18, 8324–8329 (2002).
Won, Y.Y., Brannan, A.K., Davis, H.T. & Bates, F.S. Cryogenic transmission electron microscopy (cryo-tem) of micelles and vesicles formed in water by polyethylene oxide)-based block copolymers. J. Phys. Chem. B 106, 3354–3364 (2002).
Roberts, M.J., Bentley, M.D. & Harris, J.M. Chemistry for Peptide and protein PEGylation. Adv. Drug Deliv. Rev. 54, 459–476 (2002).
Yamaoka, T., Tabata, Y. & Ikada, Y. Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice. J. Pharm. Sci. 83, 601–606 (1994).
Neuhaus, D. & Williamson, M.P. The Nuclear Overhauser Effect in Structural and Conformational Analysis (VCH, New York, 1989).
Grindel, J.M., Jaworski, T., Piraner, O., Emanuele, R.M. & Balasubramanian, M. Distribution, metabolism, and excretion of a novel surface-active agent, purified poloxamer 188, in rats, dogs, and humans. J. Pharm. Sci. 91, 1936–1947 (2002).
Fukami, A. & Adachi, K. On a new preparation method of a self-perforated micro plastic grid. J. Electron. Microsc. 13, 52 (1964).
Dubochet, J. et al. Cryo-electron microscopy of vitrified specimens. Q. Rev. Biophys. 21, 129–228 (1988).
Egelhaaf, S.U., Schurtenberger, P. & Muller, M. New controlled environment vitrification system for cryo-transmission electron microscopy: design and application to surfactant solutions. J. Microsc-Oxford 200, 128–139 (2000).
Claridge, T.D.W. in High-Resolution NMR Techniques in Organic Chemistry (eds. Baldwin, J.E., Williams, F.R.S. & Williams, R.M.) Ch. 5 (Elsevier Science, Oxford, 1999).
Price, W.S. Pulsed-field gradient nuclear magnetic resonance as a tool for studying translational diffusion: Part II. Experimental aspects. Concepts Magn. Res. 10, 197–237 (1998).
Price, W.S. Pulsed-field gradient nuclear magnetic resonance as a tool for studying translational diffusion.1. Basic theory. Concepts Magn. Res. 9, 299–336 (1997).
Boss, B.D., Stejskal, E.O. & Ferry, J.D. Self-diffusion in high molecular weight polyisobutylene-benzene mixtures determined by pulsed-gradient spin-echo method. J. Phys. Chem.-US 71, 1501–1506 (1967).
This research was supported in part by a grant from the Research Commission of the Swiss Federal Institute of Technology. Authors acknowledge Anita Saraf for the preliminary experimental work on copolymer oxidation, and Heinz Rüegger at ETH Zurich for discussions on NMR results.
The authors declare no competing financial interests.
About this article
Cite this article
Napoli, A., Valentini, M., Tirelli, N. et al. Oxidation-responsive polymeric vesicles. Nature Mater 3, 183–189 (2004) doi:10.1038/nmat1081
Journal of Controlled Release (2020)
Ginsenoside Rg3-loaded, reactive oxygen species-responsive polymeric nanoparticles for alleviating myocardial ischemia-reperfusion injury
Journal of Controlled Release (2020)
Advanced Therapeutics (2019)
Macromolecular Rapid Communications (2019)
Polymer Reviews (2019)