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Magnetic field remotely controlled selective biocatalysis

Abstract

Many applications for medical therapy, biotechnology and biosensors rely on efficient delivery and release of active substances. Here, we demonstrate a platform that explores magnetic-field-responsive compartmentalization of biocatalytic reactions for well-controlled release of chemicals or biological materials on demand. This platform combines two different kinds of core–shell magnetic nanoparticle: one loaded with enzymes and another with substrate-bound therapeutic (bio)chemicals. Both cargos are shielded with a polymer brush structure of the nanoparticle shell, which prevents any enzyme–substrate interactions. The shield’s barrier is overcome when a relatively weak (a fraction of 1 T) external magnetic field is applied and the enzyme and the substrate are merged and forced to interact in the generated nanocompartment. The merged biocatalytic nanoparticles liberate the substrate-bound therapeutic drugs when the enzymes degrade the substrate. The developed platform provides a proof of concept for the remotely controlled release of drugs or (bio)chemicals using the energy of a non-invasive, weak magnetic field.

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Fig. 1: E- and S-type superparamagnetic nanoparticles carrying the enzyme and the substrate.
Fig. 2: Monitoring of the magnetic-field-triggered release of fluorescein dye.
Fig. 3: Chains of biocatalytic nanoparticles.
Fig. 4: Magnetically controlled release of the drug.
Fig. 5: Magnetic-field-triggered blocking of cancer cell proliferation.
Fig. 6: Magnetic-field-triggered biocatalysis in the cell culture.

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Acknowledgements

The authors would like to thank the National Science Foundation (grant number DMR 1426193) for funding. We would like to thank D. Asheghali, J. Xie and L. Xie, University of Georgia, USA for providing the mouse 4T1 breast tumour cells and assistance with cell culture experiments. We would also like to thank T. Enright, University of Georgia for assistance with NPs synthesis and functionalization and valuable discussions.

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Authors

Contributions

S.M. and E.K. conceived the central ideas and directed the project. A.Z. synthesized and characterized the NPs, studied their biocatalytic behaviour in a magnetic field including in the presence of cell culture; A.M.L. contributed to the characterization of the NPs and conjugation of proteins; N.G. performed experiments with the confocal microscope. All authors contributed to the analysis of the results and commented on the manuscript.

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Correspondence to Sergiy Minko.

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The authors declare no competing financial interests.

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Supplementary Information

Supplementary Methods, Supplementary Figs. 1–19, Supplementary Tables 1–3, Supplementary References

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Zakharchenko, A., Guz, N., Laradji, A.M. et al. Magnetic field remotely controlled selective biocatalysis. Nat Catal 1, 73–81 (2018). https://doi.org/10.1038/s41929-017-0003-3

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