Modeling receptor-mediated endocytosis of polymer-functionalized iron oxide nanoparticles by human macrophages

Lunov, Oleg; Zablotskii, V.; Syrovets, Tatiana; Röcker, Carlheinz; Tron, Kyrylo; Nienhaus, G. Ulrich; Simmet, Thomas

doi:10.1016/j.biomaterials.2010.08.111

Cited by 146 publications

(141 citation statements)

References 43 publications

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“…Previous USPIO accumulation studies have used macrophages treated with USPIO in concentrations ranging from 50 to 500 mg Fe/mL and for time periods lasting from 1 to 72 h (14)(15)(16)(17). On the basis of our preliminary study findings, macrophages were incubated with USPIO (400 mg Fe/mL) for the last 16 h of the 2-d treatment with polarizing stimulus at 37°C in 5% CO 2 (Fig.…”

Section: Uspio Accumulation In M1 and M2 Macrophagesmentioning

confidence: 99%

Comparison of Contrast Agents for Atherosclerosis Imaging Using Cultured Macrophages: FDG Versus Ultrasmall Superparamagnetic Iron Oxide

et al. 2013

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Various noninvasive imaging methods have been developed to evaluate atherosclerotic plaques. Among them, 18 F-FDG PET and MR imaging with ultrasmall superparamagnetic iron oxide particles (USPIO) have been used to quantify plaque inflammation. Both methods are based on the efficient uptake of FDG and USPIO by macrophages in atherosclerotic lesions. Differently polarized macrophages have been reported to have different characteristics that are involved in the pathologic development of atherosclerosis. M1 polarized macrophages are considered the more proatherogenic phenotype than M2 polarized macrophages. However, little is known regarding the association between macrophage polarization and FDG or USPIO accumulation. In this study, we investigated intracellular FDG and USPIO accumulation in M1 and M2 polarized macrophages. Methods: THP-1 macrophages were differentiated into M1 and M2 polarized macrophages. Under optimal glucose conditions, we investigated the 3 H-labeled FDG uptake in M1 and M2 polarized macrophages. We then investigated intracellular USPIO uptake by M1 and M2 macrophages. Results: We found that M1 polarization, compared with M2 polarization, results in increased intracellular accumulation of FDG. To elucidate the mechanism by which FDG was preferentially accumulated in M1 macrophages, we examined messenger RNA expressions of glucose transporters (GLUTs) and hexokinases, which have pivotal roles in glucose uptake, and glucose-6-phosphatase (G6Pase), which catalyzes the reverse reaction of hexokinase. In M1 macrophages, GLUT-1, GLUT-3, hexokinase 1, and hexokinase 2 were upregulated and G6Pase was downregulated. In contrast to FDG, M1 polarization resulted in decreased intracellular accumulation of USPIO. We found that scavenger receptor A and CD11b, which are involved in USPIO binding and uptake, were significantly downregulated by M1 polarization. Conclusion: Compared with M2, proatherogenic M1 macrophages preferentially accumulated FDG but not USPIO, suggesting that FDG PET is a useful method for the detection of proinflammatory M1 macrophages.

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Section: Uspio Accumulation In M1 and M2 Macrophagesmentioning

confidence: 99%

Comparison of Contrast Agents for Atherosclerosis Imaging Using Cultured Macrophages: FDG Versus Ultrasmall Superparamagnetic Iron Oxide

et al. 2013

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“…A number of cationic NPs have been indicated to enter cells by transiently generating holes in the cell membrane (43). However, most of the uptake of NPs into mammalian cells and macrophages usually occurs via endocytosis (44,45). In the present study, TEM indicated that the platinum-tethered NPs synthesized in the present study were internalized by SGC-7901 cells via endocytosis.…”

Section: Cellular Uptake and Cytotoxicity Of Oxaliplatin-au-fe 3 O 4 mentioning

confidence: 45%

Target‑specific delivery of oxaliplatin to HER2‑positive gastric cancer cells inï¿½vivo using oxaliplatin‑au‑fe3o4‑herceptin nanoparticles

Liu

Chen

et al. 2018

Oncol Lett

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Abstract. Gastric cancer is the fourth most common malignancy globally. In order to decrease the dosage and side effects of conventional chemotherapy, and achieve improved benefits from molecular targeted therapy, novel drug delivery systems were developed in the present study. Oxaliplatin-Au-Fe 3 O 4 -Herceptin ® acts as a dual-functional nanoparticles (NPs) conjugate and possesses the capability of human epithelial growth factor receptor 2 (HER2) targeting and oxaliplatin delivery. The 8-20 nm Au-Fe 3 O 4 were synthesized by decomposing iron pentacarbonyl on the surfaces of Au NPs in the presence of oleic acid and oleylamine. Following being coated with polyethylene glycol, the NPs possessed a ζ-potential of 13.8±1.6 mV and were demonstrated to exhibit no cytotoxicity when Fe concentration is <100 µg/ml via an MTS assay. Mass spectrometry analysis detected a peak at m/z 148,000, and Nuclear Magnetic Resonance indicated peaks at δ 3.51 (8.00H, s, 3-H), 2.97-3.02 (3.80H, t, 2-H) and 2.72-2.76 (3.72H, t, 1-H) following successful loading with Herceptin and oxaliplatin probes. A drug release assay via dialysis cassettes demonstrated that 25% of the oxaliplatin was released at pH 8.0, however >58% was released at pH 6.0 following 4 h incubation, indicating its pH-dependent release characteristic. The active targeting feature of oxaliplatin-Au-Fe 3 O 4 -Herceptin was verified in a subcutaneous xenograft mouse model containing SGC-7901 cells via detecting aggregated low intensity in T 2 -weighted magnetic resonance imaging, which was further confirmed by immunohistochemistry. Therefore, oxaliplatin-Au-Fe 3 O 4 -Herceptin is a promising multifunctional platform for simultaneous magnetic traceable and HER2 targeted chemotherapy for gastric cancer.

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“…In this model, only the ther modynamic aspect information can be obtained without the dynamic process [110]. In contrast to molecular modeling simulations, Lunov et al proposed a mathematic model to investigate the receptormediated endocytosis of engineered NPs by macrophages, which showed key parameters of this process (e.g., rate of uptake, the number of NPs per cell in saturation and the mean uptake time) [111]. They presented the understanding of NM-cell interactions in a more macroscopic way than the dynamic method.…”

Section: Mathematical and Numerical Modeling Approaches For Nm-biomembrmentioning

confidence: 99%

Advances in The Understanding of Nanomaterial–Biomembrane Interactions and Their Mathematical and Numerical Modeling

Lin

et al. 2013

Nanomedicine

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The widespread application of nanomaterials (NMs), which has accompanied advances in nanotechnology, has increased their chances of entering an organism, for example, via the respiratory system, skin absorption or intravenous injection. Although accumulating experimental evidence has indicated the important role of NM–biomembrane interaction in these processes, the underlying mechanisms remain unclear. Computational techniques, as an alternative to experimental efforts, are effective tools to simulate complicated biological behaviors. Computer simulations can investigate NM–biomembrane interactions at the nanoscale, providing fundamental insights into dynamic processes that are challenging to experimental observation. This paper reviews the current understanding of NM–biomembrane interactions, and existing mathematical and numerical modeling methods. We highlight the advantages and limitations of each method, and also discuss the future perspectives in this field. Better understanding of NM–biomembrane interactions can benefit various fields, including nanomedicine and diagnosis.

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Modeling receptor-mediated endocytosis of polymer-functionalized iron oxide nanoparticles by human macrophages

Cited by 146 publications

References 43 publications

Comparison of Contrast Agents for Atherosclerosis Imaging Using Cultured Macrophages: FDG Versus Ultrasmall Superparamagnetic Iron Oxide

Comparison of Contrast Agents for Atherosclerosis Imaging Using Cultured Macrophages: FDG Versus Ultrasmall Superparamagnetic Iron Oxide

Target‑specific delivery of oxaliplatin to HER2‑positive gastric cancer cells inï¿½vivo using oxaliplatin‑au‑fe3o4‑herceptin nanoparticles

Advances in The Understanding of Nanomaterial–Biomembrane Interactions and Their Mathematical and Numerical Modeling

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