Dynamic development of the protein corona on silica nanoparticles: composition and role in toxicity

Ninell P. Mortensen; Gregory B. Hurst; Wei Wang; Carmen M. Foster; Prakash D. Nallathamby; Scott T. Retterer

doi:10.1039/C3NR33280B

Dynamic development of the protein corona on silicananoparticles: composition and role in toxicity†

Ninell P. Mortensen,^abef Gregory B. Hurst,^c Wei Wang,^d Carmen M. Foster,^a Prakash D. Nallathamby^e and Scott T. Retterer*^abe

Author affiliations

* Corresponding authors

^a Biological and Nanoscale Systems Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA
E-mail: rettererst@ornl.gov

^b Center for Nanophase Materials Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA

^c Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA

^d Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA

^e B-FAST, Battelle Center for Fundamental and Applied Systems Toxicology, Battelle Memorial Institute, Columbus, OH, USA

^f Nanotoxicology & Nanopharmacology, Center for Aerosol & Nanomaterials Engineering, RTI International, RTP, NC, USA

Abstract

The formation and composition of the protein corona on silica (SiO₂) nanoparticles (NP) with different surface chemistries was evaluated over time. Native SiO₂, amine (–NH₂) and carboxy (–COO⁻) modified NP were examined following incubation in mammalian growth media containing fetal bovine serum (FBS) for 1, 4, 24 and 48 hours. The protein corona transition from its early dynamic state to the later more stable corona was evaluated using mass spectrometry. The NP diameter was 22.4 ± 2.2 nm measured by scanning transmission electron microscopy (STEM). Changes in hydrodynamic diameter and agglomeration kinetics were studied using dynamic light scattering (DLS). The initial surface chemistry of the NP played an important role in the development and final composition of the protein corona, impacting agglomeration kinetics and NP toxicity. Particle toxicity, indicated by changes in membrane integrity and mitochondrial activity, was measured by lactate dehydrogenase (LDH) release and tetrazolium reduction (MTT), respectively, in mouse alveolar macrophages (RAW264.7) and mouse lung epithelial cells (C10). SiO₂–COO⁻ NP had a slower agglomeration rate, formed smaller aggregates, and exhibited lower cytotoxicity compared to SiO₂ and SiO₂–NH₂. Composition of the protein corona for each of the three NP was unique, indicating a strong dependence of corona development on NP surface chemistry. This work underscores the need to understand all aspects of NP toxicity, particularly the influence of agglomeration on effective dose and particle size. Furthermore, the interplay between materials and local biological environment is emphasized and highlights the need to conduct toxicity profiling under physiologically relevant conditions that provide an appropriate estimation of material modifications that occur during exposure in natural environments.

Nanoscale

Dynamic development of the protein corona on silicananoparticles: composition and role in toxicity†

Abstract

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Dynamic development of the protein corona on silica nanoparticles: composition and role in toxicity

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