Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

Abstract

The efficient entry of nanotechnology-based pharmaceuticals into target cells is highly desired to reach high therapeutic efficiency while minimizing the side effects. Despite intensive research, the impact of the surface coating on the mechanism of nanoparticle uptake is not sufficiently understood yet. Herein, we present a mechanistic study of cellular internalization pathways of two magnetic iron oxide nanoparticles (MNPs) differing in surface chemistry into A549 cells. The MNP uptake was investigated in the presence of different inhibitors of endocytosis and monitored by spectroscopic and imaging techniques. The results revealed that the route of MNP entry into cells strongly depends on the surface chemistry of the MNPs. While serum bovine albumin-coated MNPs entered the cells via clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis (CavME) or lipid rafts were preferentially involved in the internalization of polyethylene glycol-coated MNPs. Our data indicate that surface engineering can contribute to an enhanced delivery efficiency of nanoparticles.

Unveiling the interplay between homogeneous and heterogeneous catalytic mechanisms in copper–iron nanoparticles working under chemically relevant tumour conditions

“…However surface coating also plays a key role, since for Fe x O y NPs coated with BSA and PEG, clathrin- or caveolin-mediated endocytosis were favoured, respectively. 84 Moreover, the use of DMSA as coating agent has been also reported as a way to boost the uptake efficiency for Fe 2 O 3 NPs. 85 …”

“…However surface coating also plays a key role, since for Fe x O y NPs coated with BSA and PEG, clathrin-or caveolin-mediated endocytosis were favoured, respectively. 84 Moreover, the use of DMSA as coating agent has been also reported as a way to boost the uptake efficiency for Fe 2 O 3 NPs. 85 Up to now, the interaction between Cu and Fe based nanoparticles and GSH has been either interpreted from the perspective of a heterogeneous process taking place at the nanoparticle-liquid interface or directly neglected.…”

Delivery and assessment of a CRISPR/nCas9-based genome editing system on in vitro models of mucopolysaccharidoses IVA assisted by magnetite-based nanoparticles

“…1 E), strongly suggesting endocytosis as the main uptake mechanism 49 , 50 . Additional experiments will be needed to elucidate if classical clathrin- or caveolin-related pathways might be involved in the MNPs@Ag-pD/BUF-II internalization, as described for similar nanostructures 51 – 53 .…”

Plate reader spectroscopy as an alternative to atomic absorption spectroscopy for the assessment of nanoparticle cellular uptake

“…For PRS measurements, cells were seeded onto 6-well plates (Ø = 35 mm) at a density of 2 × 10 5 cells/well. After 24 h, cells were pre-treated in a culture medium with 2% FCS for 24 h. Cells were then exposed to various non-toxic concentrations [ 25 , 26 ] of BSA–SO–MNPs (herein expressed as μg of Fe 3 O 4 per mL) ranging between 0-116 μg Fe 3 O 4 /mL for 5 h in culture medium with 2% FCS. After exposure, cells were washed with phosphate-buffered saline (PBS; Thermo Fisher Scientific, USA), trypsinized, counted, and pelleted (200 × g , 5 min).…”

“…The metallic core enabled parallel quantification of NPs by AAS. Since lungs are well-known to accumulate iron oxide NPs [ 25 , 26 ], intracellular uptake of BSA–SO–MNPs was evaluated in human alveolar epithelial cancer cell line A549.…”