Mechanism of Iron Oxide-Induced Macrophage Activation: The Impact of Composition and the Underlying Signaling Pathway

Gu, Zhengying; Liu, Tianqing; Tang, Jie; Yang, Yannan; Song, Hao; Tuong, Zewen Kelvin; Fu, Joseph; Yu, Chengzhong

doi:10.1021/jacs.8b10904

Cited by 151 publications

(151 citation statements)

References 36 publications

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“…There is a complex interdependence between the physicochemical properties of nanomaterials and their catalytic activity. [ 41,42 ] Regarding iron oxide NPs, the surface Fe 2+ ions play an important role for their peroxidase‐like activity. [ 17 ] Therefore, Fe 2 O 3 NPs showed an inferior catalytic activity compared to Fe 3 O 4 NPs (Figure 6b) due to the diminished amount of Fe 2+ ions on the surface of iron oxide NPs.…”

Section: Discussionmentioning

confidence: 99%

Peroxidase‐Like Nanozymes Induce a Novel Form of Cell Death and Inhibit Tumor Growth In Vivo

Wang

Liu

et al. 2020

Adv Funct Materials

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Nanomaterials with intrinsic enzyme-like properties, termed nanozymes, have attracted significant interest, although limited information is available on their biological characteristics in cells or in vivo. Here, it is shown that nanomaterials with peroxidase-like activity trigger a novel form of cell death through an ATP-citrate lyase (ACLY)-dependent rat sarcoma viral oncogene (RAS) signaling mechanism. The peroxidase nanozyme-induced cell lethality, which is termed as nanoptosis, is morphologically and biochemically distinct from the currently well-defined apoptosis, necrosis, autophagy, pyroptosis, and ferroptosis. It is revealed that nanoptosis is typically characterized by the massive accumulation of cellular vesicles, swelling mitochondria, and distinct chromatin condensation and margination. Using RNA sequencing and protein quantitative mass spectrometry, an ACLY-dependent RAS signaling pathway is identified that mainly mediates this nanozyme lethality process, and it is observed that RAS-knockout cells are highly resistant to nanoptosis. Finally, it is demonstrated that this newly discovered nanozyme lethality can be used as an effective therapeutic strategy for inhibiting tumor growth in vivo.

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Section: Discussionmentioning

confidence: 99%

Peroxidase‐Like Nanozymes Induce a Novel Form of Cell Death and Inhibit Tumor Growth In Vivo

Wang

Liu

et al. 2020

Adv Funct Materials

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“…In keeping with these findings, in a mouse model of sickle disease, hemolysis and macrophage heme-iron accumulation trigger a proinflammatory phenoytpe in hepatic macrophages (Vinchi et al., 2016). In cancer, iron-loaded tumor-associated macrophages adopt a pro-inflammatory phenotype that can directly kill tumor cells (Costa da Silva et al., 2017), and the usage of iron oxide nanoparticles is an attractive avenue in cancer immunotherapy through the modulation of macrophage activity (Gu et al., 2019, Zanganeh et al., 2016). In summary, the findings from all of the above-mentioned studies converge toward a macrophage polarization profile resulting from prolonged exposure to iron in the tissue microenvironment, correlating with a pro-inflammatory (M1-like) phenotype.…”

Section: Introductionmentioning

confidence: 99%

Acute Iron Deprivation Reprograms Human Macrophage Metabolism and Reduces Inflammation In Vivo

et al. 2019

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Summary Iron is an essential metal that fine-tunes the innate immune response by regulating macrophage function, but an integrative view of transcriptional and metabolic responses to iron perturbation in macrophages is lacking. Here, we induced acute iron chelation in primary human macrophages and measured their transcriptional and metabolic responses. Acute iron deprivation causes an anti-proliferative Warburg transcriptome, characterized by an ATF4-dependent signature. Iron-deprived human macrophages show an inhibition of oxidative phosphorylation and a concomitant increase in glycolysis, a large increase in glucose-derived citrate pools associated with lipid droplet accumulation, and modest levels of itaconate production. LPS polarization increases the itaconate:succinate ratio and decreases pro-inflammatory cytokine production. In rats, acute iron deprivation reduces the severity of macrophage-dependent crescentic glomerulonephritis by limiting glomerular cell proliferation and inducing lipid accumulation in the renal cortex. These results suggest that acute iron deprivation has in vivo protective effects mediated by an anti-inflammatory immunometabolic switch in macrophages.

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“…It has been reported that SPIONs affect cytokine production in immune cells, including macrophages (Hsiao et al., 2008; Yeh et al., 2010). In addition, several reports have shown that SPIONs induce a phenotypic shift in macrophages from M2 to M1 (Laskar et al., 2013; Gu et al., 2019). Therefore, we evaluated the effect of magnetic lipoplexes on cytokine and NO production in RAW264 cells.…”

Section: Discussionmentioning

confidence: 99%

Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field

et al. 2019

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Magnetically guided cell delivery systems would be valuable to achieve effective macrophage-based cell therapy for colonic inflammatory diseases. In the current study, we developed a method for the efficient and simultaneous introduction of superparamagnetic iron oxide nanoparticles (SPIONs) and plasmid DNA (pDNA) into RAW264 murine macrophage-like cells using SPION-incorporated cationic liposome/pDNA complexes (magnetic lipoplexes). SPIONs and pDNA were introduced for magnetization and functionalization of the macrophages, respectively. We also evaluated the adhesive properties of magnetized RAW264 cells using magnetic lipoplexes in the murine colon under a magnetic field. Significant cellular association and gene expression without cytotoxicity were observed when magnetic cationic liposomes and pDNA were mixed at a weight ratio of 10:1, and SPION concentration and magnetic field exposure time was 0.1 mg/mL and 10 min, respectively. We also observed that cytokine production in magnetized RAW264 cells was similar to that in non-treated RAW264 cells, whereas nitric oxide production was significantly increased in magnetized RAW264 cells. Furthermore, magnetized RAW264 cells highly adhered to a Caco-2 cell monolayer and colon in mice, under a magnetic field. These results suggest that this magnetic cell delivery system can improve the colonic delivery of macrophages and its therapeutic efficacy against colonic inflammatory diseases.

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Mechanism of Iron Oxide-Induced Macrophage Activation: The Impact of Composition and the Underlying Signaling Pathway

Cited by 151 publications

References 36 publications

Peroxidase‐Like Nanozymes Induce a Novel Form of Cell Death and Inhibit Tumor Growth In Vivo

Peroxidase‐Like Nanozymes Induce a Novel Form of Cell Death and Inhibit Tumor Growth In Vivo

Acute Iron Deprivation Reprograms Human Macrophage Metabolism and Reduces Inflammation In Vivo

Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field

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