The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages

Lunov, Oleg; Syrovets, Tatiana; Büchele, Berthold; Jiang, Xiue; Röcker, Carlheinz; Tron, Kyrylo; Nienhaus, G. Ulrich; Walther, Paul; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

doi:10.1016/j.biomaterials.2010.03.023

Cited by 144 publications

(114 citation statements)

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“…Although iron oxide nanoparticles have been reported to affect the functionality of T cells and antigen-presenting cells, [12][13][14][15][16]18,19,23,24 evidence pertaining to their effects on Th1 cell-mediated immunity in vivo remains mostly unknown. It was previously reported that systemic administration of ovalbumin-sensitized mice with iron oxide nanoparticles suppresses, the serum production of ovalbumin-specific immunoglobulin G1 and immunoglobulin G2a, and the expression of both IFN-γ and IL-4 by splenocytes.…”

Section: Discussionmentioning

confidence: 99%

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Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Shen¹,

Liang²,

Liao³

et al. 2012

IJN

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Background: It was recently reported that iron oxide nanoparticles attenuated antigen-specific humoral responses and T cell cytokine expression in ovalbumin-sensitized mice. It is presently unclear whether iron oxide nanoparticles influence T helper 1 cell-mediated immunity. The present study aimed to investigate the effect of iron oxide nanoparticles on delayed-type hypersensitivity (DTH), whose pathophysiology requires the participation of T helper 1 cells and macrophages. Methods: DTH was elicited by a subcutaneous challenge with ovalbumin to the footpads of mice sensitized with ovalbumin. Iron oxide nanoparticles (0.2-10 mg iron/kg) were administered intravenously 1 hour prior to ovalbumin sensitization. Local inflammatory responses were examined by footpad swelling and histological analysis. The expression of cytokines by splenocytes was measured by enzyme-linked immunosorbent assay. Results: Administration of iron oxide nanoparticles, in a dose-dependent fashion, significantly attenuated inflammatory reactions associated with DTH, including the footpad swelling, the infiltration of T cells and macrophages, and the expression of interferon-γ, interleukin-6, and tumor necrosis factor-α in the inflammatory site. Iron oxide nanoparticles also demonstrated a suppressive effect on ovalbumin-stimulated production of interferon-γ by splenocytes and the phagocytic activity of splenic CD11b + cells. Conclusion:These results demonstrated that a single dose of iron oxide nanoparticles attenuated DTH reactions by suppressing the infiltration and functional activity of T helper 1 cells and macrophages in response to antigen stimulation.

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Section: Discussionmentioning

confidence: 99%

“…Exposure of primary macrophages to iron oxide nanoparticles results in a marked induction of oxidative stress and apoptosis. 13 In addition, iron oxide nanoparticles suppress the phagocytic activity of RAW 264.7 cells -a murine macrophage line -and increase the production of tumor necrosis factor-α (TNF-α) and nitric oxide.…”

Section: Introductionmentioning

confidence: 99%

Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Shen¹,

Liang²,

Liao³

et al. 2012

IJN

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“…53 However, this could result in high accumulation of iron in the liver for an extended time. Lunov et al 55 reported that SPIONs triggered increased ROS production, followed by sustained activation of c-Jun N-terminal kinase (JNK) and production of pro-inflammatory cytokine tumor necrosis factor alpha (TNF-a) that led to the apoptosis of Kupffer cells. This was partially due to the Fenton reaction, in which the released ferrous ions (Fe 2+ ) have a high potential for reacting with hydrogen peroxide and oxygen produced by the mitochondria to form highly reactive hydroxyl radicals that could induce oxidative stress, leading to DNA, protein, and lipid damages.…”

Section: Spionsmentioning

confidence: 99%

Facilitating Translational Nanomedicine via Predictive Safety Assessment

et al. 2017

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Extensive research on engineered nanomaterials (ENMs) has led to the development of numerous nano-based formulations for theranostic purposes. Although some nano-based drug delivery systems already exist on the market, growing numbers of newly designed ENMs exhibit improved physicochemical properties and are being assessed in preclinical stages. While these ENMs are designed to improve the efficacy of current nanobased therapeutic or imaging systems, it is necessary to thoroughly determine their safety profiles for successful clinical applications. As such, our aim in this mini-review is to discuss the current knowledge on predictive safety and structure-activity relationship (SAR) analysis of major ENMs at the developing stage, as well as the necessity of additional long-term toxicological analysis that would help to facilitate their transition into clinical practices. We focus on how the interaction of these nanomaterials with cells would trigger signaling pathways as molecular initiating events that lead to adverse outcomes. These mechanistic understandings would help to design safer ENMs with improved therapeutic efficacy in clinical settings.During the past decades, engineered nanomaterials (ENMs) have been widely used in biomedical applications, such as nanomedicine, bioimaging, and tissue engineering, because of their unique biophysicochemical properties.1,2 With regard to nanomedicine applications, ENMs could be formulated as drug carriers that deliver the therapeutic reagents within the human body and increase their bioavailability and blood circulation half-life.2 Moreover, these nanocarriers could be functionalized to deliver the drug specifically to the desired target tissues (e.g., tumors) and release the payload sustainably over long periods, thereby eliminating the necessity of multiple drug administration and reducing its cytotoxic side effects toward healthy cells.2 In addition to their implementation in drug delivery, ENMs could be used for diagnostic and imaging purposes that would help to monitor the disease and administer the treatment more accurately. 2Past research in nanomedicine has led to the design of various nanomaterial-based therapeutic and diagnostic systems that are being investigated in experimental stages (e.g., in vitro and in vivo) and clinical trials or are commercially available to the corresponding patients (Table 1). Most commercialized nanomaterial-based therapeutic reagents use lipids, proteins, and polymers that could self-assemble and biodegrade with few side effects.3 Because of high biocompatibility of lipids, several commercial liposome-drug formulations have been developed, mostly relying on polyethylene glycol (PEG)-conjugated lipids, such as DOXIL, AmBisome, Epaxal, and Inflexal V, and are under clinical trials focusing on various types of disease treatments. 4,5 Polymer-based nanoparticles (NPs) also present low toxicity, but their surface functionalization may affect their safety. The most commonly used materials include PEG, ploy(lactic-co-glycolic) acid (PLGA...

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“…Research on human macrophages treated with ferucarbotran show increased apoptosis after 120 hours of incubation even at the concentration of 1 ug Fe/mL. Human macrophage also shows apoptotic change when facing smaller MNPs, supravist, a smaller particle of 20.8 nm in diameter, for 120 hours at the concentration of 0.1 ug Fe/mL (Lunov et al, 2010a). The apoptotic event is inducted by N-terminal kinase (JNK) pathway that is activated by reactive oxygen species (Lunov et al, 2010a;2010b).…”

Section: Impact Of Magnetic Nanoparticles In Immunologic Cellmentioning

confidence: 99%

“…Human macrophage also shows apoptotic change when facing smaller MNPs, supravist, a smaller particle of 20.8 nm in diameter, for 120 hours at the concentration of 0.1 ug Fe/mL (Lunov et al, 2010a). The apoptotic event is inducted by N-terminal kinase (JNK) pathway that is activated by reactive oxygen species (Lunov et al, 2010a;2010b). There is evidence that elevated TNF-alpha induce human macrophage apoptosis after these macrophages expose to ferucarbotran for 3-5 days.…”

Section: Impact Of Magnetic Nanoparticles In Immunologic Cellmentioning

confidence: 99%

Magnetic Nanoparticles: Its Effect on Cellular Behaviour and Potential Applications

Liu¹,

Hsiao²

2012

Smart Nanoparticles Technology

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The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages

Cited by 144 publications

References 59 publications

Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Facilitating Translational Nanomedicine via Predictive Safety Assessment

Magnetic Nanoparticles: Its Effect on Cellular Behaviour and Potential Applications

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