Abstract
Stimuli-responsive hydrogels that undergo abrupt changes in volume in response to external stimuli such as pH, temperature and solvent composition have potential applications in biomedicine and the creation of ‘intelligent’ materials systems, for example as media for drug delivery, separation processes and protein immobilization. Hydrogels have been reported that respond to pH1,2,3,, temperature4,5,6,7,8,9,10,11,12,13, electric fields14,15,16, saccharides17,18,19,20,21,22,. For some biomedical applications it would be very useful to have a material whose swelling response was dictated by a specific protein. Here we report such a material, which swells reversibly in a buffer solution in response to a specific antigen. The hydrogel was prepared by grafting the antigen and corresponding antibody to the polymer network, so that binding between the two introduces crosslinks in the network. Competitive binding of the free antigen triggers a change in gel volume owing to breaking of these non-covalent crosslinks. In addition, we show that the hydrogel displays shape-memory behaviour, and that stepwise changes in antigen concentration can induce pulsatile permeation of a protein through the network.
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References
Tanaka, T. Collapse of gels and the critical endpoint. Phys. Rev. Lett. 40, 820–823 (1978).
Tanaka, T. et al. Phase transitions in ionic gels. Phys. Rev. Lett. 45, 1636–1639 (1980).
Siegel, R. A. & Firestone, B. A. pH-dependent equilibrium swelling properties of hydrophobic polyelectrolyte copolymer gels. Macromolecules 21, 3254–3259 (1988).
Hirokawa, Y. & Tanaka, T. Volume phase transition in a nonionic gel. J. Chem. Phys. 81, 6379–6380 (1984).
Hoffman, A. S. Applications of thermally reversible polymers and hydrogels in therapeutics and diagnostics. J. Controlled Release 6, 297–305 (1987).
Bae, Y. H., Okano, T., Hsu, R. & Kim, S. W. Thermo-sensitive polymers as on-off switches for drug release. Makromol. Chem. Rapid Commun. 8, 481–485 (1987).
Bae, Y. H., Okano, T. & Kim, S. W. Anew thermo-sensitive hydrogel: interpenetrating polymer networks from N-acryloylpyrrolidine and poly(oxyethylene). Makromol. Chem. Rapid Commun. 9, 185–189 (1988).
Chen, G. & Hoffman, A. S. Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 373, 49–52 (1995).
Yoshida, R. et al. Comb-type grafted hydrogels with rapid de-swelling response to temperature changes. Nature 374, 240–242 (1995).
Miyata, T., Nakamae, K., Hoffman, A. S. & Kanzaki, Y. Stimuli-sensitivities of hydrogels containing phosphate groups. Macromol. Chem. Phys. 195, 1111–1120 (1994).
Aoki, T. et al. Temperature-responsive interpenetrating polymer networks constructed with poly(acrylic acid) and poly(N,N -dimethylacrylamide). Macromolecules 27, 947–952 (1994).
Stayton, P. S. et al. Control of protein-ligand recognition using a stimuli-responsive polymer. Nature 378, 472–474 (1995).
Feil, H., Bae, Y. H., Feijen, J. & Kim, S. W. Molecular separation by thermosensitive hydrogel membranes. J. Membrane Sci. 64, 283–294 (1991).
Tanaka, T., Nishio, I., Sun, S.-T. & Ueno-Nishio, S. Collapse of gels in an electric field. Science 218, 467–469 (1982).
Kwon, I. C., Bae, Y. H. & Kim, S. W. Electrically erodible polymer gel for controlled release of drugs. Nature 354, 291–293 (1991).
Osada, Y., Okuzaki, H. & Hori, H. Apolymer gel with electrically driven motility. Nature 355, 242–244 (1992).
Kokufuta, E., Zhang, Y.-Q. & Tanaka, T. Saccharide-sensitive phase transition of a lectin-loaded gel. Nature 351, 302–304 (1991).
Miyata, T., Jikihara, A., Nakamae, K. & Hoffman, A. S. Preparation of poly(glucosyloxyethyl methacrylate)-concanavalin A complex hydrogel and its glucose-sensitivity. Macromol. Chem. Phys. 197, 1135–1146 (1996).
Lee, S. J. & Park, K. Synthesis and characterization of sol-gel phase-reversible hydrogels sensitive to glucose. J. Mol. Recogn. 9, 549–557 (1996).
Obidat, A. A. & Park, K. Characterization of glucose dependent gel-sol phase transition of polymeric glucose-concanavalin A hydrogel system. Pharm. Res. 13, 989–995 (1996).
Obidat, A. A. & Park, K. Characterization of protein release through glucose-sensitive hydrogel membranes. Biomaterials 18, 801–806 (1997).
Kataoka, K. et al. Totally synthetic polymer gels responding to external glucose concentration: their preparation and application to on-off regulation of insulin release. J. Am. Chem. Soc. 120, 12694–12695 (1998).
Shoemaker, S. G., Hoffman, A. S. & Priest, J. H. Synthesis and properties of vinyl monomer/enzyme conjugates. Appl. Biochem. Biotech. 15, 11–24 (1987).
Natsume, T. et al. Interactions between collagen-binding stress protein HSP47 and collagen. J. Biol. Chem. 269, 31224–31228 (1994).
Murai, N., Taguchi, H. & Yoshida, M. Kinetic analysis of interactions between GroEL and reduced α-lactalbumin. J. Biol. Chem. 270, 19957–19963 (1995).
Flory, P. J. Principles of Polymer Chemistry(Cornell Univ. Press, New York, 1953).
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Miyata, T., Asami, N. & Uragami, T. A reversibly antigen-responsive hydrogel. Nature 399, 766–769 (1999). https://doi.org/10.1038/21619
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DOI: https://doi.org/10.1038/21619
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