Differential Internalization of Superparamagnetic Iron Oxide Nanoparticles in Different Types of Cells

Xu, Haowen; Dai, Wei; Han, Yehua; Hao, Wei; Xiong, Fei; Cao, Ji‐Min

doi:10.1166/jnn.2010.2830

Cited by 15 publications

(12 citation statements)

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“…Between each cell line, the 3T3 cells exhibited the highest fluorescence intensity at each time point. This result suggests that the membrane composition of the 3T3 cells is more permeable to the particles [33].…”

Section: Resultsmentioning

confidence: 86%

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Dynamic Cellular Uptake of Mixed-Monolayer Protected Nanoparticles

Carney

Mueller

et al. 2012

Biointerphases

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Nanoparticles (NPs) are gaining increasing attention for potential application in medicine; consequently, studying their interaction with cells is of central importance. We found that both ligand arrangement and composition on gold nanoparticles play a crucial role in their cellular internalization. In our previous investigation, we showed that 66-34OT nanoparticles coated with stripe-like domains of hydrophobic (octanethiol, OT, 34%) and hydrophilic (11-mercaptoundecane sulfonate, MUS, 66%) ligands permeated through the cellular lipid bilayer via passive diffusion, in addition to endo-/pino-cytosis. Here, we show an analysis of NP internalization by DC2.4, 3T3, and HeLa cells at two temperatures and multiple time points. We study four NPs that differ in their surface structures and ligand compositions and report on their cellular internalization by intracellular fluorescence quantification. Using confocal laser scanning microscopy we have found that all three cell types internalize the 66-34OT NPs more than particles coated only with MUS, or particles coated with a very similar coating but lacking any detectable ligand shell structure, or 'striped' particles but with a different composition (34-66OT) at multiple data points.

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Section: Resultsmentioning

confidence: 86%

“…In this study, we introduce 3T3 mouse fibroblasts and the human HeLa cervical cancer cell line. Care was taken to choose three unique cell lines that were known to exhibit differences in phenotype, cell division times, and endocytotic uptake [31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Dynamic Cellular Uptake of Mixed-Monolayer Protected Nanoparticles

Carney

Mueller

et al. 2012

Biointerphases

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“…Suppression of I K and I K1 channels by MWCNTs [9] may also rationally contribute to APD prolongation in cardiomyocytes if confirmed. Second, we showed that MWCNTs need to enter the cell to affect the I to channel, while the endocytotic process for nanomaterials entering cells with low phagocytotic capacity usually takes an hour or longer [34]. However, MWCNTs intravenous infusion soon (within minutes) induced bradyarrhythmias.…”

Section: Discussionmentioning

confidence: 94%

Multi-Walled Carbon Nanotubes Impair Kv4.2/4.3 Channel Activities, Delay Membrane Repolarization and Induce Bradyarrhythmias in the Rat

et al. 2014

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PurposeThe potential hazardous effects of multi-walled carbon nanotubes (MWCNTs) on cardiac electrophysiology are seldom evaluated. This study aimed to investigate the impacts of MWCNTs on the Kv4/I to channel, action potential and heart rhythm and the underlying mechanisms.MethodsHEK293 cells were engineered to express Kv4.2 or Kv4.3 with or without KChIP2 expression. A series of approaches were introduced to analyze the effects of MWCNTs on Kv4/I to channel kinetics, current densities, expression and trafficking. Transmission electron microscopy was performed to observe the internalization of MWCNTs in HEK293 cells and rat cardiomyocytes. Current clamp was employed to record the action potentials of isolated rat cardiomyocytes. Surface ECG and epicardial monophasic action potentials were recorded to monitor heart rhythm in rats in vivo. Vagal nerve discharge monitoring and H&E staining were also performed.ResultsInduction of MWCNTs into the cytosole through pipette solution soon accelerated the decay of I Kv4 in HEK293 cells expressing Kv4.2/4.3 and KChIP2, and promoted the recovery from inactivation when Kv4.2 or Kv4.3 was expressed alone. Longer exposure (6 h) to MWCNTs decreased the I Kv4.2 density, Kv4.2/Kv4.3 (but not KChIP2) expression and trafficking towards the plasma membrane in HEK293 cells. In acutely isolated rat ventricular myocytes, pipette MWCNTs also quickly accelerated the decay of I Kv4 and prolonged the action potential duration (APD). Intravenous infusion of MWCNTs (2 mg/rat) induced atrioventricular (AV) block and even cardiac asystole. No tachyarrhythmia was observed after MWCNTs administration. MWCNTs did not cause coronary clot but induced myocardial inflammation and increased vagus discharge.ConclusionsMWCNTs suppress Kv4/I to channel activities likely at the intracellular side of plasma membrane, delay membrane repolarization and induce bradyarrhythmia. The delayed repolarization, increased vagus output and focal myocardial inflammation may partially underlie the occurrence of bradyarrhythmias induced by MWCNTs. The study warns that MWCNTs are hazardous to cardiac electrophysiology.

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“…The NPs can be efficiently internalized by a variety of cell types through a combination of uptake routes, including, but not limited to, clathrin-mediated endocytosis (CME), caveolar endocytosis, macropinocytosis and, in specialized cells, phagocytosis (Ivanov 2008;Sahay, Alakhova, and Kabanov 2010;Gu et al 2011;Zhao et al 2011;Kafshgari, Harding, and Voelcker 2015). In macrophage cells multiple endocytotic mechanisms have previously been found responsible for the internalization of SPIONs, including CME, caveolae dependent mechanisms, macropinocytosis and phagocytosis (Raynal et al 2004;Xu et al 2010;Gu et al 2011;Lunov et al 2011;Schlorf et al 2010;Yang et al 2011). The internalization of SPIONs into macrophage models has been widely studied compared to non-macrophage cell types.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms for cellular uptake of nanosized clinical MRI contrast agents

2020

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Engineered Nanomaterials (NMs), such as Superparamagnetic Iron Oxide Nanoparticles (SPIONs), offer significant benefits in a wide range of applications, including cancer diagnostic and therapeutic strategies. However, the use of NMs in biomedicine raises safety concerns due to lack of knowledge on possible biological interactions and effects. The initial basis for using SPIONs as biomedical MRI contrast enhancement agents was the idea that they are selectively taken up by macrophage cells, and not by the surrounding cancer cells. To investigate this claim, we analyzed the uptake of SPIONs into well-established cancer cell models and benchmarked this against a common macrophage cell model. In combination with fluorescent labeling of compartments and siRNA silencing of various proteins involved in common endocytic pathways, the mechanisms of internalization of SPIONs in these cell types has been ascertained utilizing reflectance confocal microscopy. Caveolar mediated endocytosis and macropinocytosis are both implicated in SPION uptake into cancer cells, whereas in macrophage cells, a clathrin-dependant route appears to predominate. Colocalization studies confirmed the eventual fate of SPIONs as accumulation in the degradative lysosomes. Dissolution of the SPIONs within the lysosomal environment has also been determined, allowing a fuller understanding of the cellular interactions, uptake, trafficking and effects of SPIONs within a variety of cancer cells and macrophages. Overall, the behavior of SPIONS in non-phagocytotic cell lines is broadly similar to that in the specialist macrophage cells, although some differences in the uptake patterns are apparent. ARTICLE HISTORY

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Differential Internalization of Superparamagnetic Iron Oxide Nanoparticles in Different Types of Cells

Cited by 15 publications

References 0 publications

Dynamic Cellular Uptake of Mixed-Monolayer Protected Nanoparticles

Dynamic Cellular Uptake of Mixed-Monolayer Protected Nanoparticles

Multi-Walled Carbon Nanotubes Impair Kv4.2/4.3 Channel Activities, Delay Membrane Repolarization and Induce Bradyarrhythmias in the Rat

Mechanisms for cellular uptake of nanosized clinical MRI contrast agents

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