Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues

Zanganeh, Saeid; Hütter, Gregor; Spitler, Ryan; Lenkov, Olga; Mahmoudi, Morteza; Shaw, Aubie; Pajarinen, Jukka; Nejadnik, Hossein; Goodman, Stuart B.; Moseley, Michael E.; Coussens, Lisa M.; Daldrup-Link, Heike E.

doi:10.1038/nnano.2016.168

Cited by 1,251 publications

(998 citation statements)

References 41 publications

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“…NAC (Beyotime) was dissolved in deionized water at a concentration of 8 mmol/L, and 2.5‐mg ferrous citrate or ferric citrate was dissolved in 1 mL threefold distilled water and then filtered with a 0.2‐μm filter to ensure sterility. The concentration of iron was used as previously described to avoid cytotoxicity 12. A p300/CBP inhibitor (Abcam) was dissolved in dimethyl sulfoxide (DMSO; Thermo Fisher Scientific) at a concentration of 25 mmol/L in up to 3 μL per 1 mL medium to prevent cytotoxicity from high concentrations of DMSO.…”

Section: Methodsmentioning

confidence: 99%

“…However, the expression of iron metabolism‐related proteins in M2 macrophages is different than that in M1 macrophages 1. Another study12, 13 showed that increasing levels of intracellular iron induced polarization of proinflammation macrophages. The results of these studies suggest that regulating iron concentration in macrophages may be a novel and effective strategy for cancer immunotherapy.…”

Section: Introductionmentioning

confidence: 98%

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Iron overloaded polarizes macrophage to proinflammation phenotype through ROS/acetyl‐p53 pathway

et al. 2018

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PurposeMacrophages play critical roles in inflammation and wound healing and can be divided into two subtypes: classically activated (M1) and alternatively activated (M2) macrophages. Macrophages also play important roles in regulating iron homeostasis, and intracellular iron accumulation induces M1‐type macrophage polarization which provides a potential approach to tumor immunotherapy through M2 tumor‐associated macrophage repolarization. However, the mechanisms underlying iron‐induced M1 polarization remain unclear.MethodsWestern blotting, qRT‐PCR, and flow cytometry were used to detect the polarization indexes in RAW 264.7 murine macrophages treated with iron, and Western bloting and qRT‐PCR were used to detect p21 expression. The compound 2,7‐dichlorofluorescein diacetate was used to measure reactive oxygen species (ROS) levels in macrophages after iron or N‐acetyl‐l‐cysteine (NAC) treatment. The p300/CREB‐binding protein (CBP) inhibitor C646 was used to inhibit p53 acetylation, and Western bloting, qRT‐PCR, and immunofluorescence were used to detect p53 expression and acetylation. BALB/c mice were subcutaneously injected with H22 hepatoma cells, and macrophage polarization status was investigated after tail intravenous injection of iron. Immunohistochemical staining was used to evaluate the protein expression of cluster of differentiation 86 (CD86) and EGF‐like module‐containing mucin‐like hormone receptor‐like 1 (F4/80) in the subcutaneous tumors.ResultsIron overload induced M1 polarization by increasing ROS production and inducing p53 acetylation in RAW cells, and reduction in ROS levels by NAC repressed M1 polarization and p53 acetylation. Inhibition of acetyl‐p53 by a p300/CBP inhibitor prevented M1 polarization and inhibited p21 expression. These results showed that high ROS levels induced by iron overload polarized macrophages to the M1 subtype by enhancing p300/CBP acetyltransferase activity and promoting p53 acetylation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Iron overloaded polarizes macrophage to proinflammation phenotype through ROS/acetyl‐p53 pathway

et al. 2018

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“…[5][6][7] Recently, it has been found that iron oxide nanoparticles are even capable of inhibiting tumor growth by stimulating macrophages. 8 The properties of SPIONs are known to be size dependent, and consequently, the effect that they produce on tissues is varied. 9,10 Another important parameter responsible for toxicity of the SPIONs is the shape of these nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Low toxic maghemite nanoparticles for theranostic applications

Kuchma¹,

Zolotukhin²,

Belanova³

et al. 2017

IJN

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Background Iron oxide nanoparticles have numerous and versatile biological properties, ranging from direct and immediate biochemical effects to prolonged influences on tissues. Most applications have strict requirements with respect to the chemical and physical properties of such agents. Therefore, developing rational design methods of synthesis of iron oxide nanoparticles remains of vital importance in nanobiomedicine. Methods Low toxic superparamagnetic iron oxide nanoparticles (SPIONs) for theranostic applications in oncology having spherical shape and maghemite structure were produced using the fast microwave synthesis technique and were fully characterized by several complementary methods (transmission electron microscopy [TEM], X-ray diffraction [XRD], dynamic light scattering [DLS], X-ray photoelectron spectroscopy [XPS], X-ray absorption near edge structure [XANES], Mossbauer spectroscopy, and HeLa cells toxicity testing). Results TEM showed that the majority of the obtained nanoparticles were almost spherical and did not exceed 20 nm in diameter. The averaged DLS hydrodynamic size was found to be ~33 nm, while that of nanocrystallites estimated by XRD waŝ16 nm. Both XRD and XPS studies evidenced the maghemite (γ-Fe 2 O 3 ) atomic and electronic structure of the synthesized nanoparticles. The XANES data analysis demonstrated the structure of the nanoparticles being similar to that of macroscopic maghemite. The Mossbauer spectroscopy revealed the γ-Fe 2 O 3 phase of the nanoparticles and vibration magnetometry study showed that reactive oxygen species in HeLa cells are generated both in the cytoplasm and the nucleus. Conclusion Quasispherical Fe 3+ SPIONs having the maghemite structure with the average size of 16 nm obtained by using the fast microwave synthesis technique are expected to be of great value for theranostic applications in oncology and multimodal anticancer therapy.

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“…Advances in nanotechnology have improved the ability to develop and specifically tailor the microstructural features and properties of functional, structural and biomaterials for high tech applications [1][2][3][4][5][6]. In recent years, graphene, reduced graphene oxide (RGO) and functionalized graphene oxide (FGO) have been used for different applications.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Nanocomposite of Functionalized Graphene Oxide with Multi Core-Shell Fe3O4-ZnO-TiO2 Nanoparticles

Nemati¹,

Haider²,

Ghanbarnezhad³

et al. 2017

International Conference of Theoretical and Applied Nanoscience and Nanotechnology

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-This project involves development and characterization of nanocomposite of functionalized graphene oxide with multi coreshell Fe3O4-ZnO-TiO2 nanoparticles (abbreviated as G-MCSN) with enhanced multi-functional properties. The multi core-shell nanoparticles consist of superparamagnetic core with modified shells of photocatalytic materials. After synthesis of Fe3O4 nanoparticles (using co-precipitation and solvothermal processes), it was coated with multi shells of ZnO and TiO2 (via a facile sol-gel rout). Functionalized graphene oxide was synthesized and mixed with multi core-shell nanoparticles to prepare the nanocomposite. The phases and morphology of the core-shell nanoparticles and the nanocomposite were investigated by X-ray diffraction (XRD), field emission scanning electron microscopy (FE/SEM) and transmission electron microscopy (TEM/SAED). The magnetization hysteresis curves of the samples were conducted by a vibrating sample magnetometer (VSM). The results showed that the average size of synthesized magnetite nanoparticles were less than 20 nm. The précised control of the procedure resulted in the formation of core-shell structure after coating with ZnO and TiO2. The median size of core-shell nanoparticles was less than 50 nm. TEM studies revealed the formation of a few layers functionalized graphene oxide (FGO), as well as core-shell nanoparticles. Vibrating sample magnetometer measurement showed that magnetic property of the core-shell nanoparticles was lower than the bare Fe3O4 nanoparticles (from 40.96 emu.g -1 in bare Fe3O4 nanoparticles to 20.13 and 12.98 emu.g -1 in core-shell nanoparticles). But, when nanocomposite was made (FGO with core-shell nanoparticles), magnetic property was increased in comparison with the coreshell nanoparticles from 12.98 emu.g -1 to 28.18 emu.g -1 .

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Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues

Cited by 1,251 publications

References 41 publications

Iron overloaded polarizes macrophage to proinflammation phenotype through ROS/acetyl‐p53 pathway

Iron overloaded polarizes macrophage to proinflammation phenotype through ROS/acetyl‐p53 pathway

Low toxic maghemite nanoparticles for theranostic applications

Synthesis and Characterization of Nanocomposite of Functionalized Graphene Oxide with Multi Core-Shell Fe3O4-ZnO-TiO2 Nanoparticles

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