Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology
Abstract
In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to form rapidly (<0.5 minutes) and, over time, to change significantly in terms of the amount of bound protein, but not in composition. Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time.
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These strategies are still limited at conferring targeting specificity because an additional targeting ligand increases the propensity for protein corona formation to mask targeting ability and inhibit the biological effects of nanoparticles.
“these strategies are still limited at conferring targeting specificity since an additional targeting ligand increases the propensity for protein corona formation to mask the targeting ability and inhibit the biological effects of nanoparticles18–24.”
From Cloaking nanoparticles with protein corona shield for targeted drug delivery. (2018) · cites this paper as [18]
Cites
Chauhan, V. P., Stylianopoulos, T., Martin, J. D., Popović, Z., Chen, O., Kamoun, W. S., Bawendi, M. G., Fukumura, D., & Jain, R. K. (2012) · Nature Nanotechnology · doi:10.1038/nnano.2012.45 · Cited by 1,101 · see citing works
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Engineering precision nanoparticles for drug delivery
Mitchell, M. J., Billingsley, M. M., Haley, R. M., Wechsler, M. E., Peppas, N. A., & Langer, R. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0090-8 · Cited by 7,933 · see citing works
Principles of nanoparticle design for overcoming biological barriers to drug delivery
Blanco, E., Shen, H., & Ferrari, M. (2015) · Nature Biotechnology · doi:10.1038/nbt.3330 · Cited by 7,002 · see citing works
Interactions of microplastic debris throughout the marine ecosystem
Galloway, T. S., Cole, M., & Lewis, C. (2017) · Nature Ecology & Evolution · doi:10.1038/s41559-017-0116 · Cited by 1,955 · see citing works
Emergence of Nanoplastic in the Environment and Possible Impact on Human Health
Lehner, R., Weder, C., Petri-Fink, A., & Rothen-Rutishauser, B. (2019) · Environmental Science & Technology · doi:10.1021/acs.est.8b05512 · Cited by 1,242 · see citing works
Presence of microplastics and nanoplastics in food, with particular focus on seafood
(CONTAM), E. P. O. C. I. T. F. C. (2016) · EFSA Journal · doi:10.2903/j.efsa.2016.4501 · Cited by 958 · see citing works
Pharmacokinetic aspects of retinal drug delivery
del Amo, E. M., Rimpelä, A.-K., Heikkinen, E., Kari, O. K., Ramsay, E., Lajunen, T., Schmitt, M., Pelkonen, L., Bhattacharya, M., Richardson, D., et al. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.12.001 · Cited by 693 · see citing works
Neural recording and modulation technologies
Chen, R., Canales, A., & Anikeeva, P. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2016.93 · Cited by 655 · see citing works
Altered Behavior, Physiology, and Metabolism in Fish Exposed to Polystyrene Nanoparticles
Mattsson, K., Ekvall, M. T., Hansson, L.-A., Linse, S., Malmendal, A., & Cedervall, T. (2015) · Environmental Science & Technology · doi:10.1021/es5053655 · Cited by 581 · see citing works
Micro- and nanoplastic induced cellular toxicity in mammals: A review
Banerjee, A., & Shelver, W. L. (2021) · Science of The Total Environment · doi:10.1016/j.scitotenv.2020.142518 · Cited by 492 · see citing works
The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors
Izci, M., Maksoudian, C., Manshian, B. B., & Soenen, S. J. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00779 · Cited by 506 · see citing works
A holistic approach to targeting disease with polymeric nanoparticles
Cheng, C. J., Tietjen, G. T., Saucier-Sawyer, J. K., & Saltzman, W. M. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4503 · Cited by 480 · see citing works
Wu, P., Lin, S., Cao, G., Wu, J., Jin, H., Wang, C., Wong, M. H., Yang, Z., & Cai, Z. (2022) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2022.129361 · Cited by 428 · see citing works
Cloaking nanoparticles with protein corona shield for targeted drug delivery.
Oh, J. Y., Kim, H. S., Palanikumar, L., Go, E. M., Jana, B., Park, S. A., Kim, H. Y., Kim, K., Seo, J. K., Kwak, S. K., et al. (2018) · Nature communications · doi:10.1038/s41467-018-06979-4 · Cited by 409 · see citing works
Cheng, G., Li, W., Ha, L., Han, X., Hao, S., Wan, Y., Wang, Z., Dong, F., Zou, X., Mao, Y., et al. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b03584 · Cited by 371 · see citing works
Greven, A.-C., Merk, T., Karagöz, F., Mohr, K., Klapper, M., Jovanović, B., & Palić, D. (2016) · Environmental Toxicology and Chemistry · doi:10.1002/etc.3501 · Cited by 357 · see citing works
Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver
Miao, L., Lin, J., Huang, Y., Li, L., Delcassian, D., Ge, Y., Shi, Y., & Anderson, D. G. (2020) · Nature Communications · doi:10.1038/s41467-020-16248-y · Cited by 343 · see citing works
Brain-targeted drug delivery by manipulating protein corona functions
Zhang, Z., Guan, J., Jiang, Z., Yang, Y., Liu, J., Hua, W., Mao, Y., Li, C., Lu, W., Qian, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11593-z · Cited by 334 · see citing works
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von Roemeling, C., Jiang, W., Chan, C. K., Weissman, I. L., & Kim, B. Y. S. (2017) · Trends in Biotechnology · doi:10.1016/j.tibtech.2016.07.006 · Cited by 330 · see citing works
Hesler, M., Aengenheister, L., Ellinger, B., Drexel, R., Straskraba, S., Jost, C., Wagner, S., Meier, F., von Briesen, H., Büchel, C., et al. (2019) · Toxicology in Vitro · doi:10.1016/j.tiv.2019.104610 · Cited by 291 · see citing works
Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery
Waheed, S., Li, Z., Zhang, F., Chiarini, A., Armato, U., & Wu, J. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01605-4 · Cited by 259 · see citing works
Kim, M., Chen, C., Wang, P., Mulvey, J. J., Yang, Y., Wun, C., Antman-Passig, M., Luo, H.-B., Cho, S., Long-Roche, K., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00860-y · Cited by 214 · see citing works
The viral protein corona directs viral pathogenesis and amyloid aggregation
Ezzat, K., Pernemalm, M., Pålsson, S., Roberts, T. C., Järver, P., Dondalska, A., Bestas, B., Sobkowiak, M. J., Levänen, B., Sköld, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10192-2 · Cited by 209 · see citing works
Chen, T., He, B., Tao, J., He, Y., Deng, H., Wang, X., & Zheng, Y. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.04.009 · Cited by 186 · see citing works
Bigdeli, A., Palchetti, S., Pozzi, D., Hormozi-Nezhad, M. R., Baldelli Bombelli, F., Caracciolo, G., & Mahmoudi, M. (2016) · ACS Nano · doi:10.1021/acsnano.6b00261 · Cited by 157 · see citing works
Stealth Effect of Biomolecular Corona on Nanoparticle Uptake by Immune Cells
Caracciolo, G., Palchetti, S., Colapicchioni, V., Digiacomo, L., Pozzi, D., Capriotti, A. L., La Barbera, G., & Laganà, A. (2015) · Langmuir · doi:10.1021/acs.langmuir.5b02158 · Cited by 131 · see citing works
Mild Innate Immune Activation Overrides Efficient Nanoparticle‐Mediated RNA Delivery
Lokugamage, M. P., Gan, Z., Zurla, C., Levin, J., Islam, F. Z., Kalathoor, S., Sato, M., Sago, C. D., Santangelo, P. J., & Dahlman, J. E. (2020) · Advanced Materials · doi:10.1002/adma.201904905 · Cited by 126 · see citing works
Zwitterionic PEG-PC Hydrogels Modulate the Foreign Body Response in a Modulus-Dependent Manner
Jansen, L. E., Amer, L. D., Chen, E. Y.-T., Nguyen, T. V., Saleh, L. S., Emrick, T., Liu, W. F., Bryant, S. J., & Peyton, S. R. (2018) · Biomacromolecules · doi:10.1021/acs.biomac.8b00444 · Cited by 120 · see citing works
Clinically approved liposomal nanomedicines: lessons learned from the biomolecular corona
Caracciolo, G. (2018) · Nanoscale · doi:10.1039/c7nr07450f · Cited by 106 · see citing works
Ho, Y. T., Kamm, R. D., & Kah, J. C. Y. (2018) · Nanoscale · doi:10.1039/c8nr02393j · Cited by 102 · see citing works
Characteristics of nano-plastics in bottled drinking water
Huang, Y., Wong, K. K., Li, W., Zhao, H., Wang, T., Stanescu, S., Boult, S., van Dongen, B., Mativenga, P., & Li, L. (2022) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.127404 · Cited by 84 · see citing works
Beyond the protein corona—Lipids matter for biological response of nanocarriers
Müller, J., Prozeller, D., Ghazaryan, A., Kokkinopoulou, M., Mailänder, V., Morsbach, S., & Landfester, K. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.02.036 · Cited by 79 · see citing works
Self-citationHuang, K., Boerhan, R., Liu, C., & Jiang, G. (2017) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b00726 · Cited by 74 · see citing works
Langridge, T. D., & Gemeinhart, R. A. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.12.038 · Cited by 51 · see citing works
Derakhshankhah, H., Sajadimajd, S., Jafari, S., Izadi, Z., Sarvari, S., Sharifi, M., Falahati, M., Moakedi, F., Muganda, W. C. A., Müller, M., et al. (2020) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2020.102149 · Cited by 48 · see citing works
Nanoparticle decoration impacts airborne fungal pathobiology
Westmeier, D., Solouk-Saran, D., Vallet, C., Siemer, S., Docter, D., Götz, H., Männ, L., Hasenberg, A., Hahlbrock, A., Erler, K., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804542115 · Cited by 22 · see citing works
Self-citationThe Significance and Insignificance of Carbon Nanotube-Induced Inflammation
Boyles, M., Stoehr, L., Schlinkert, P., Himly, M., & Duschl, A. (2014) · Fibers · doi:10.3390/fib2010045 · Cited by 22 · see citing works
The role of the protein Corona in fiber structure-activity relationships
Kucki, M., Kaiser, J.-P., Clift, M., Rothen-Rutishauser, B., Petri-Fink, A., & Wick, P. (2014) · Fibers · doi:10.3390/fib2030187 · Cited by 7 · see citing works
- Authors
- Tenzer, S., Docter, D., Kuharev, J., Musyanovych, A., Fetz, V., Hecht, R., Schlenk, F., Fischer, D., Kiouptsi, K., Reinhardt, C., Landfester, K., Schild, H., Maskos, M., Knauer, S. K., & Stauber, R. H.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Max Planck Institute for Polymer Research (DE)
- University of Duisburg-Essen (DE)
- Friedrich Schiller University Jena (DE)
- Corresponding author
- Tenzer, Stefan
- Stauber, Roland H.
- ORCID
- Venue
- Nature Nanotechnology
- Published
- 2013-09-22
- Volume
- 8
- Issue
- 10
- Pages
- 772-781
- ISSN
- 1748-3387 (ISSN-L)
- 1748-3395
- OpenAlex
- W1973831032
- Cited by
- 2,283
- References
- 1
- Citations by year
- 2026: 177 · 2025: 134 · 2024: 112 · 2023: 146 · 2022: 212 · 2021: 213 · 2020: 230 · 2019: 183 · 2018: 195 · 2017: 184 · 2016: 186 · 2015: 176 · 2014: 125 · 2013: 6
- FWCI
- 62.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Keywords
- protein corona, nanoparticle-protein interactions, label-free quantitative proteomics, silica nanoparticles, polystyrene nanoparticles, nanoparticle size, surface functionalization, hemolysis, platelet activation, nanoparticle uptake, endothelial cell death, human plasma
- MeSH terms
- Blood Platelets, Blood Proteins, Cell Line, Humans, Particle Size, Polystyrenes, Silicon Dioxide, Cell Death, Microscopy, Confocal, Computational Biology, Endothelial Cells, Nanoparticles, Microvessels
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