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Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona

Abstract

To promote drug delivery to exact sites and cell types, the surface of nanocarriers is functionalized with targeting antibodies or ligands, typically coupled by covalent chemistry. Once the nanocarrier is exposed to biological fluid such as plasma, however, its surface is inevitably covered with various biomolecules forming the protein corona, which masks the targeting ability of the nanoparticle. Here, we show that we can use a pre-adsorption process to attach targeting antibodies to the surface of the nanocarrier. Pre-adsorbed antibodies remain functional and are not completely exchanged or covered by the biomolecular corona, whereas coupled antibodies are more affected by this shielding. We conclude that pre-adsorption is potentially a versatile, efficient and rapid method of attaching targeting moieties to the surface of nanocarriers.

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Fig. 1: Synthesis and characterization of antibody-functionalized nanoparticles.
Fig. 2: Covalent anti-CD63-functionalized nanoparticles lose their targeting ability in the presence of the protein corona while adsorbed antibodies keep their targeting properties.
Fig. 3: Antibody adsorption is a pH-dependent process.
Fig. 4: Adsorbed antibodies are not exchanged over time in the presence of the protein corona and remain functional.

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Acknowledgements

We wish to thank the Deutsche Forschungsgemeinschaft (DFG, SFB1066) for supporting this study. Support from the Max Planck Society is also gratefully acknowledged. In addition, we would like to thank C. Siebert and C. Sauer for their technical support.

Author contributions

V.M., K.L. and D.C. supervised the project. V.M., M.T. and J.S. conceived and designed the experiments. D.E. synthesized the nanoparticles. M.K., P.R. and I.L performed the transmission electron microscopy analysis. J.R. contributed to the figure illustration and protein structure analysis. U.K. and A.K. performed the confocal electron microscopy experiments. M.P.D. and K.S. contributed with additional biological assays. All authors discussed the results and commented on the manuscript.

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Correspondence to Volker Mailänder.

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Tonigold, M., Simon, J., Estupiñán, D. et al. Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona. Nature Nanotech 13, 862–869 (2018). https://doi.org/10.1038/s41565-018-0171-6

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