Impact of the protein corona on metal oxide nanoparticle-induced toxicity mechanisms
Final Report Abstract
Not only are engineered nanomaterials (NMs) widely used in technical products, their applications are increasing in biotechnology and biomedicine, including potential pest-control approaches in the environment. Besides their desired benefits, extended exposure to NMs might also exhibit nanotoxicity and thus, potential risks for human health and ecosystems. The effects induced by a specific NM are dependent on its physicochemical characteristics as well as the (patho)physiological environments. Whereas the physico-chemical properties and behavior of NMs can be engineered and characterized under idealized conditions, this is no longer the case in complex (patho)physiological or natural environments. Here, proteins and other biomolecules rapidly bind to NMs, forming the protein/biomolecule corona potentially also affecting the NMs’ (patho)biological and biotechnological identity. As the corona impacts in vitro and/or in vivo applications of NMs in humans and ecosystems, a mechanistic comprehensive understanding of its overarching relevance and the biophysical forces regulating corona formation is mandatory, but still incomplete. Consequently, combining controlled NM models, such as metal-(oxide) and various other NMs, with state- of-the-art analytical methods, together with in vitro (co-culture) and in vivo exposure models, our project sought to gain novel insights into corona-affected processes at nano-bio interfaces, which may subsequently be exploited to design NMs with improved efficacy, safety, and biocompatibility. During our project, we comprehensively studied various novel aspects of biomolecule coronas' impact on biotechnological and biomedical applications of NMs as well as on potential risks for human health and ecosystems. Employing various analytical methods, such as electron and intravital imaging microscopy, proteomics-based corona profiling, high-content cell-based analyses and bioinformatics, together with (co- culture) in vitro and in vivo exposure models, we successfully demonstrated that: • corona formation occurred to various degrees on all tested NMs and (partially) affected their physico-chemical properties and cross-talk with nano-bio interface, including cellular machines suchas proteases/proteasome, and identified potential novel nanotoxicity mechanisms. • a wide array of NMs formed biomolecule corona-dependently complexes with fungal and bacterial pathogens, thereby affecting the microbes' (patho)biology. • Additionally, we developed and employed systematic high-content cell-based analyses to show that corona formation reduced but did not enhance NM-dependent cytotoxicity and stress responses. Corona effects seemed to be mainly due to physical shielding rather than the pathobiological impact of defined corona proteins. Collectively, the knowledge generated by our project not only improves our current understanding of basic corona-affected (toxicity) processes at nano-bio interfaces but can indeed be exploited to design NMs with improved efficacy, safety, and biocompatibility for biomedicine and biotechnology. Also, the obtained novel knowledge and experimental models form the basis for follow-up grant applications.
Publications
- 2017. Synthesis and Characterization of Stimuli-Responsive Star-Like Polypept(o)ides: Introducing Biodegradable PeptoStars. Macromol Biosci 17
Holm, R., Weber, B., Heller, P., Klinker, K., Westmeier, D., Docter, D., Stauber, R.H., Barz, M.
(See online at https://doi.org/10.1002/mabi.201600514) - 2018. Changing environments and biomolecule coronas: consequences and challenges for the design of environmentally acceptable engineered NPs. Green Chemistry 20, 4133-4168
Markiewicz, M., Kumirska, J., Lynch, I., Matzke, M., Köser, J., Bemowsky, S., Docter, D., Stauber, R.H., Westmeier, D., Stolte, S.
(See online at https://doi.org/10.1039/C8GC01171K) - 2018. Nanoparticle binding attenuates the pathobiology of gastric cancerassociated Helicobacter pylori. Nanoscale 10, 1453-1463
Westmeier, D., Posselt, G., Hahlbrock, A., Bartfeld, S., Vallet, C., Abfalter, C., Docter, D., Knauer, S.K., Wessler, S., Stauber, R.H.
(See online at https://doi.org/10.1039/c7nr06573f) - 2018. Nanoparticle decoration impacts airborne fungal pathobiology. Proc Natl Acad Sci U S A 115, 7087-7092
Westmeier, D., Solouk-Saran, D., Vallet, C., Siemer, S., Docter, D., Gotz, H., Mann, L., Hasenberg, A., Hahlbrock, A., Erler, K., Reinhardt, C., Schilling, O., Becker, S., Gunzer, M., Hasenberg, M., Knauer, S.K., Stauber, R.H.
(See online at https://doi.org/10.1073/pnas.1804542115) - 2018. Small Meets Smaller: Effects of NMs on Microbial Biology, Pathology, and Ecology. ACS Nano 12, 6351-6359
Stauber, R.H., Siemer, S., Becker, S., Ding, G.B., Strieth, S., Knauer, S.K.
(See online at https://doi.org/10.1021/acsnano.8b03241) - 2018. The effect of saliva on the fate of NPs. Clin Oral Investig 22, 929-940
Teubl, B.J., Stojkovic, B., Docter, D., Pritz, E., Leitinger, G., Poberaj, I., Prassl, R., Stauber, R.H., Frohlich, E., Khinast, J.G., Roblegg, E.
(See online at https://doi.org/10.1007/s00784-017-2172-5) - 2019. Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics. Biomaterials 192, 551-559
Siemer, S., Westmeier, D., Barz, M., Eckrich, J., Wunsch, D., Seckert, C., Thyssen, C., Schilling, O., Hasenberg, M., Pang, C., Docter, D., Knauer, S.K., Stauber, R.H., Strieth, S.
(See online at https://doi.org/10.1016/j.biomaterials.2018.11.028) - 2020. Mechanisms of nanotoxicity - Biomolecule coronas protect pathological fungi against nanoparticle-based erradiation. Nanotoxicology
Roland H. Stauber , Dana Westmeier , Madita Wandrey , Sven Becker , Dominic Docter , Guo-Bin Ding , Eckhard Thines , Shirley K. Knauer & Svenja Siemer
(See online at https://doi.org/10.1080/17435390.2020.1808251) - 2020. The Other Side of the Corona: NPs Inhibit the Protease Taspase1 in a Size- Dependent Manner. Nanoscale
van den Boom, J., Hensel, A., Trusch, F., Matena, A., Siemer, S., Guel, D., Docter, D., Höing, A., Bayer, P., Stauber, R.H., Knauer, S.K.
(See online at https://doi.org/10.1039/d0nr01631d)
