Corona Composition Can Affect the Mechanisms Cells Use to Internalize Nanoparticles

Abstract

Nanosized objects, such as nanoparticles and other drug carriers used in nanomedicine, once in contact with biological environments are modified by adsorption of biomolecules on their surface. The presence of this corona strongly affects the following interactions at cell and organism levels. It has been shown that corona proteins can be recognized by cell receptors. However, it is not known whether the composition of this acquired layer can also affect the mechanisms nanoparticles use to enter cells. This is of particular importance when considering that the same nanoparticles can form different coronas for instance in vitro when exposed to cells in different serum amounts or in vivo depending on the exposure or administration route. Thus, in this work, different coronas were formed on 50 nm silica by exposing them to different serum concentrations. The uptake efficiency in HeLa cells was compared, and the uptake mechanisms were characterized using transport inhibitors and RNA interference. The results showed that the nanoparticles were internalized by cells via different mechanisms when different coronas were formed, and only for one corona condition was uptake mediated by the LDL receptor. This suggested that coronas of different composition can be recognized differently by cell receptors, and this in turn leads to internalization via different mechanisms. Similar studies were performed using other cells, including A549 cells and primary HUVEC, and different nanoparticles, namely 100 nm liposomes and 200 nm silica. Overall, the results confirmed that the corona composition can affect the mechanisms of nanoparticle uptake by cells.

Protein Corona Composition of Silica Nanoparticles in Complex Media: Nanoparticle Size does not Matter

“…These latter 2 of 15 form a so-called "protein corona" on NPs' surfaces [11]. The composition of the corona was shown to have an impact on NPs' biodistribution [12], susceptibility to biodegradation [13], cell internalization mechanism [14], and the immune response they trigger [15]. Consequently, the composition of this corona can lead to detrimental effects regarding the target specificity of nano-carriers used in nanomedicine [16].…”

Molecular Mechanisms, Characterization Methods, and Utilities of Nanoparticle Biotransformation in Nanosafety Assessments

“…Besides, ESI-MS is well compatible to separation techniques like the liquid chromatography(LC), which is able to acquire massive information of a complex biological samples, such as various biomolecules in coronas. [146,148,149,159,[162][163][164] Beside of the identification of adsorbed biomolecules on ENM surfaces, MS could be explored to examine the chemical structure changes of biomolecules reacting with ENMs, e.g., the stripping of phosphate groups as well as oxidation of unsaturated lipids by rare earth oxides and GO NPs. [21,33,72] In our recent work, LC-MS was utilized to detect the transferring of hydrogen from lactic and malic acids catalyzed by 2D tin selenide (SnSe) nanosheets.…”

“…Recent progresses of mass spectrometry methods toward biomolecules have significantly contributed in identification of corona structures. [146,159,164] Tenzer et al determined almost 300 different proteins on silica and polystyrene NPs with varied sizes and surface decorations.…”

Dye-doped silica nanoparticles: synthesis, surface chemistry and bioapplications

“…The presence of serum in cell culture media used for in vitro studies is now regarded as a key experimental parameter as it can influence cellular responses to NP exposure (Francia et al 2019). Scrutiny of experimental conditions is therefore important and, in the case of in vitro experiments conducted in the absence of serum, caution should be taken when interpreting NP-cell interactions.…”