Identification of Receptor Binding to the Biomolecular Corona of Nanoparticles

Lara, Sandra; Alnasser, Fatima; Polo, Ester; Garry, David; Giudice, Cristina Lo; Hristov, Delyan R.; Rocks, Louise; Salvati, Anna; Yan, Yan; Dawson, Kenneth A.

doi:10.1021/acsnano.6b07933

Cited by 206 publications

(207 citation statements)

References 47 publications

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“…This finding confirms that many factors shaping BC exist leading to different BCs. Our suggestion is supported by recent literature showing that LDL-enriched NPs present functional motifs that allow recognition by LDL receptor 38 . Our future biological understanding of how NPs interact with cells will confirm these conclusions more in depth by benefiting from a detailed knowledge of the arrangements of functional motifs of BC components at the nanoscale 39–41 .…”

Section: Resultssupporting

confidence: 88%

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles

et al. 2017

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Following exposure to biological milieus (e.g. after systemic administration), nanoparticles (NPs) get covered by an outer biomolecular corona (BC) that defines many of their biological outcomes, such as the elicited immune response, biodistribution, and targeting capabilities. In spite of this, the BC role in regulating the cellular uptake and the subcellular trafficking properties of NPs has remained elusive. Here, we tackle this issue by employing multicomponent (MC) lipid NPs, human plasma (HP) and HeLa cells as models for nanoformulation, biological fluid, and target cell (respectively). By confocal fluorescence microscopy experiments and image correlation analyses, we quantitatively demonstrate that the BC promotes a neat switch of cell entry mechanism and subsequent intracellular trafficking, from macropinocytosis to clathrin-dependent endocytosis. Nano liquid chromatography tandem mass spectrometry identifies Apolipoproteins as the most abundant components of the BC tested here. Interestingly, this class of proteins target the LDL receptors, which are overexpressed in clathrin-enriched membrane domains. Our results highlight the crucial role of BC as an intrinsic trigger of specific NP-cell interactions and biological responses and set the basis for a rational exploitation of the BC for targeted delivery.

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Section: Resultssupporting

confidence: 88%

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles

et al. 2017

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“…Since these molecules stay for longer times than the characteristic timescale of a given biological process, their presence is relevant for the biological identity of the nanoparticles. 28,29 The soft corona on the other hand could be exchanged within seconds. These interactions are crucial and it should not be forgotten though that it is challenging to separate the two in a biological context.…”

Section: Resultsmentioning

confidence: 99%

Visualization of the protein corona: towards a biomolecular understanding of nanoparticle-cell-interactions

et al. 2017

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The use of nanocarriers in biology and medicine is complicated by the current need to understand how nanoparticles interact in complex biological surroundings. When nanocarriers come into contact with serum, proteins immediately adsorb onto their surface, forming a protein corona which defines their biological identity. Although the composition of the protein corona has been widely determined by proteomics, its morphology still remains unclear. In this study we show for the first time the morphology of the protein corona using transmission electron microscopy. We are able to demonstrate that the protein corona is not, as commonly supposed, a dense, layered shell coating the nanoparticle, but an undefined, loose network of proteins. Additionally, we are now able to visualize and discriminate between the soft and hard corona using centrifugation-based separation techniques together with proteomic characterization. The protein composition of the ∼15 nm hard corona strongly depends on the surface chemistry of the respective nanomaterial, thus further affecting cellular uptake and intracellular trafficking. Large diameter protein corona resulting from pre-incubation with soft corona or Apo-A1 inhibits cellular uptake, confirming the stealth-effect mechanism. In summary, the knowledge on protein corona formation, composition and morphology is essential to design therapeutic effective nanoparticle systems.

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“…This observation was further supported by the viability test that, contrary to what observed with cells cultured in serum‐free medium (Figure b), showed a significant cytotoxic effect of citrate‐coated AgNPs also when NIH‐3T3 cells were cultured in medium supplemented only with 1% (v/v) FBS (Figure S10c, Supporting Information). These results reveal that adsorption of SPs on citrate‐coated AgNPs is essential for their stabilization in cell culture media and, as also recently reported for silica NPs, mediates their interaction with cell membrane, leading to their uptake and cytotoxic effect.…”

Section: Resultsmentioning

confidence: 99%

Protein Corona Mediated Uptake and Cytotoxicity of Silver Nanoparticles in Mouse Embryonic Fibroblast

Barbalinardo

Caicci

Cavallini

et al. 2018

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100

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Medical applications of nanoparticles (NPs) require understanding of their interactions with living systems in order to control their physiological response, such as cellular uptake and cytotoxicity. When NPs are exposed to biological fluids, the adsorption of extracellular proteins on the surface of NPs, creating the so-called protein corona, can critically affect their interactions with cells. Here, the effect of surface coating of silver nanoparticles (AgNPs) on the adsorption of serum proteins (SPs) and its consequence on cellular uptake and cytotoxicity in mouse embryonic fibroblasts are shown. In particular, citrate-capped AgNPs are internalized by cells and show a time- and dose-dependent toxicity, while the passivation of the NP surface with an oligo(ethylene glycol) (OEG)-alkanethiol drastically reduces their uptake and cytotoxicity. The exposure to growth media containing SPs reveals that citrate-capped AgNPs are promptly coated and stabilized by proteins, while the AgNPs resulting from capping with the OEG-alkanethiol are more resistant to adsorption of proteins onto their surface. Using NIH-3T3 cultured in serum-free, the key role of the adsorption of SPs onto surface of NPs is shown as only AgNPs with a preformed protein corona can be internalized by the cells and, consequently, carry out their inherent cytotoxic activity.

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Identification of Receptor Binding to the Biomolecular Corona of Nanoparticles

Cited by 206 publications

References 47 publications

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles

An apolipoprotein-enriched biomolecular corona switches the cellular uptake mechanism and trafficking pathway of lipid nanoparticles

Visualization of the protein corona: towards a biomolecular understanding of nanoparticle-cell-interactions

Protein Corona Mediated Uptake and Cytotoxicity of Silver Nanoparticles in Mouse Embryonic Fibroblast

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