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<p>The fate of nanomaterials in living organisms is significantly influenced by their molecular corona, which dictates their interactions with cells. For instance, silica nanoparticles (SiO<sub>2</sub>NP) form biomolecular coronas when exposed to biological fluids, thereby affecting their uptake and cytotoxicity. Understanding these dynamic interactions is crucial to optimize their use in biomedical applications. In this work, the interaction of 18&#xa0;nm SiO<sub>2</sub>NP with DMEM supplemented with FBS varying the molar concentration and time incubation in order to clarify the binding mechanism between biomolecules and nanoparticle surface. In addition, cytotoxic effects have been evaluated using the HUV-EC-C cell lineage, which plays a pivotal role during tissue repair. Biomolecular corona is formed on SiO<sub>2</sub>NP upon contact with biomolecules, generating agglomerates by association with other particles, forming colloidally stable, prolate-shaped SiO<sub>2</sub>NP@biomolecule structures, whose sizes are modified by the SiO<sub>2</sub>NP/bioprotein ratio and incubation time. Polar interactions and partial hydrophobic contributions, driven by enthalpy and entropy, controlled the formation of the dynamic SiO<sub>2</sub>NP@biomolecule agglomerates, as confirmed by isothermal titration calorimetry. These interactions alter the fluorescence quenching mechanism of tryptophan residues in the biomolecular corona as well as the cellular uptake efficiency. Cells actively interact with SiO<sub>2</sub>NP@biomolecule agglomerates leading to morphological changes and reduced viability/proliferation, depending on nanoparticle concentration. Uptake is modulated by the size of the SiO<sub>2</sub>NP@biomolecule agglomerates determined by the SiO<sub>2</sub>NP/biomolecule ratio and incubation time. Significant cytotoxicity was observed and cell population was halved after 24&#xa0;h and 48&#xa0;h when incubated respectively with 9.8&#xa0;mM and 4.6&#xa0;mM of SiO<sub>2</sub>NP. However, sublethal doses allowed cellular recovery upon nanoparticle removal. Concluding, our findings suggest that SiO₂NP bioactivity can be modulated by the SiO₂NP/biomolecule ratio and incubation time under the tested conditions, enabling control on cytotoxicity to inhibit cellular expansion, showing the importance of surface chemistry and functionalization in the development of nanomaterials for biomedical applications.</p>

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Formation of Bioprotein Corona on Silica Nanoparticles and its Impact on Cellular Responses

  • 期刊论文

  • 发表日期：

    2025年11月13日

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  • Cristofher Victor Vivas,
  • Gabriel Braga Marques Teobaldo,
  • Matheus Pirez Cortez,
  • Sergio Hiroshi Toma,
  • Jonnatan Julival dos Santos,
  • Luis Cartagena,
  • Cristiano Luis Pinto de Oliveira,
  • Iolanda Midea Cuccovia,
  • Koiti Araki,
  • Antonio Carlos Bloise,
  • Adriano Mesquita Alencar

摘要

The fate of nanomaterials in living organisms is significantly influenced by their molecular corona, which dictates their interactions with cells. For instance, silica nanoparticles (SiO2NP) form biomolecular coronas when exposed to biological fluids, thereby affecting their uptake and cytotoxicity. Understanding these dynamic interactions is crucial to optimize their use in biomedical applications. In this work, the interaction of 18 nm SiO2NP with DMEM supplemented with FBS varying the molar concentration and time incubation in order to clarify the binding mechanism between biomolecules and nanoparticle surface. In addition, cytotoxic effects have been evaluated using the HUV-EC-C cell lineage, which plays a pivotal role during tissue repair. Biomolecular corona is formed on SiO2NP upon contact with biomolecules, generating agglomerates by association with other particles, forming colloidally stable, prolate-shaped SiO2NP@biomolecule structures, whose sizes are modified by the SiO2NP/bioprotein ratio and incubation time. Polar interactions and partial hydrophobic contributions, driven by enthalpy and entropy, controlled the formation of the dynamic SiO2NP@biomolecule agglomerates, as confirmed by isothermal titration calorimetry. These interactions alter the fluorescence quenching mechanism of tryptophan residues in the biomolecular corona as well as the cellular uptake efficiency. Cells actively interact with SiO2NP@biomolecule agglomerates leading to morphological changes and reduced viability/proliferation, depending on nanoparticle concentration. Uptake is modulated by the size of the SiO2NP@biomolecule agglomerates determined by the SiO2NP/biomolecule ratio and incubation time. Significant cytotoxicity was observed and cell population was halved after 24 h and 48 h when incubated respectively with 9.8 mM and 4.6 mM of SiO2NP. However, sublethal doses allowed cellular recovery upon nanoparticle removal. Concluding, our findings suggest that SiO₂NP bioactivity can be modulated by the SiO₂NP/biomolecule ratio and incubation time under the tested conditions, enabling control on cytotoxicity to inhibit cellular expansion, showing the importance of surface chemistry and functionalization in the development of nanomaterials for biomedical applications.