Abstract
Enzyme therapeutics have great potential for the treatment of systemic disorders such as urolithiasis and nephrocalcinosis, which are caused by the excessive accumulation of oxalate. However, exogenous enzymes have short half-lives in vivo and elicit high immunogenicity, which largely limit the therapeutic outcomes. Herein, we report a delivery strategy whereby therapeutic enzymes are encapsulated within a thin zwitterionic polymer shell to form enzyme nanocapsules. The strategy is exemplified by the encapsulation of oxalate oxidase (OxO) for the treatment of hyperoxaluria, because as-synthesized OxO nanocapsules have a prolonged blood circulation half-life and elicit reduced immunogenicity. Our design of enzyme nanocapsules that enable the systemic delivery of therapeutic enzymes can be extended to various biomedical applications.
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Hoppe, B.; Beck, B. B.; Milliner, D. S. The primary hyperoxalurias. Kidney Int. 2009, 75: 1264–1271.
Karaolanis, G.; Lionaki, S.; Moris, D.; Palla, V. V.; Vernadakis, S. Secondary hyperoxaluria: A risk factor for kidney stone formation and renal failure in native kidneys and renal grafts. Transplant. Rev. 2014, 28: 182–187.
Rumsby, G. Biochemical and genetic diagnosis of the primary hyperoxalurias: A review. Mol. Urol. 2000, 4: 349–354.
Beck, B. B.; Hoyer-Kuhn, H.; Göbel, H.; Habbig, S.; Hoppe, B. Hyperoxaluria and systemic oxalosis: An update on current therapy and future directions. Expert Opin. Investig. Drugs 2013, 22: 117–129.
Bobrowski, A. E.; Langman, C. B. Hyperoxaluria and systemic oxalosis: Current therapy and future directions. Expert Opin. Pharmacother. 2006, 7: 1887–1896.
Woo, E. J.; Dunwell, J. M.; Goodenough, P. W.; Marvier, A. C.; Pickersgill, R. W. Germin is a manganese containing homohexamer with oxalate oxidase and superoxide dismutase activities. Nat. Struct. Biol. 2000, 7: 1036–1040.
Whittaker, M. M.; Pan, H. Y.; Yukl, E. T.; Whittaker, J. W. Burst kinetics and redox transformations of the active site manganese ion in oxalate oxidase: Implications for the catalytic mechanism. J. Biol. Chem. 2007, 282: 7011–7023.
Whittaker, M. M.; Whittaker, J. W. Characterization of recombinant barley oxalate oxidase expressed by Pichia pastoris. J. Biol. Inorg. Chem. 2002, 7: 136–145.
Liu, Y.; Li, J.; Lu, Y. F. Enzyme therapeutics for systemic detoxification. Adv. Drug. Deliver Rev. 2015, 90: 24–39.
Gerngross, T. U. Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nat. Biotechnol. 2004, 22: 1409–1414.
Zhang, H.; Fu, H.; Luallen, R. J.; Liu, B. F.; Lee, F. H.; Doms, R. W.; Geng, Y. Antibodies elicited by yeast glycoproteins recognize HIV-1 virions and potently neutralize virions with high mannose N-glycans. Vaccine 2015, 33: 5140–5147.
Raghavan, K. G.; Tarachand, U. Degradation of oxalate in rats implanted with immobilized oxalate oxidase. FEBS Lett. 1986, 195: 101–105.
Dahiya, T.; Pundir, C. S. In vivo oxalate degradation by liposome encapsulated oxalate oxidase in rat model of hyperoxaluria. Indian J. Med. Res. 2013, 137: 136–141.
Liang, S.; Liu, Y.; Jin, X.; Liu, G.; Wen, J.; Zhang, L. L.; Li, J.; Yuan, X. B.; Chen, I. S. Y.; Chen, W. et al. Phosphorylcholine polymer nanocapsules prolong the circulation time and reduce the immunogenicity of therapeutic proteins. Nano Res. 2016, 9: 1022–1031.
Zhang, P.; Sun, F.; Tsao, C.; Liu, S. J.; Jain, P.; Sinclair, A.; Hung, H. C.; Bai, T.; Wu, K.; Jiang, S. Y. Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity. Proc. Natl. Acad. Sci. USA 2015, 112: 12046–12051.
Jin, Q.; Chen, Y. J.; Wang, Y.; Ji, J. Zwitterionic drug nanocarriers: A biomimetic strategy for drug delivery. Colloid Surface B: Biointerfaces 2014, 124: 80–86.
Keefe, A. J.; Jiang, S. Y. Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity. Nat. Chem. 2012, 4: 59–63.
Zhao, H. Effect of ions and other compatible solutes on enzyme activity, and its implication for biocatalysis using ionic liquids. J. Mol. Catal. B: Enzym. 2005, 37: 16–25.
Li, J.; Jin, X.; Liu, Y.; Li, F.; Zhang, L. L.; Zhu, X. Y.; Lu, Y. F. Robust enzyme-silica composites made from enzyme nanocapsules. Chem. Commun. 2015, 51: 9628–9631.
Moro, T.; Takatori, Y.; Ishihara, K.; Konno, T.; Takigawa, Y.; Matsushita, T.; Chung, U. I.; Nakamura, K.; Kawaguchi, H. Surface grafting of artificial joints with a biocompatible polymer for preventing periprosthetic osteolysis. Nat. Mater. 2004, 3: 829–836.
Walkey, C. D.; Olsen, J. B.; Guo, H. B.; Emili, A.; Chan, W. C. W. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J. Am. Chem. Soc. 2012, 134: 2139–2147.
Rodriguez, P. L.; Harada, T.; Christian, D. A.; Pantano, D. A.; Tsai, R. K.; Discher, D. E. Minimal “self” peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science 2013, 339: 971–975.
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Support for OxO enzyme production from the National Institutes of Health (GM 42680) is gratefully acknowledged.
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Zhao, M., Xu, D., Wu, D. et al. Nanocapsules of oxalate oxidase for hyperoxaluria treatment. Nano Res. 11, 2682–2688 (2018). https://doi.org/10.1007/s12274-017-1898-3
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DOI: https://doi.org/10.1007/s12274-017-1898-3