Dataset Information

Macrophage-biomimetic porous Se@SiO₂ nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

ABSTRACT:

Background

Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO₂-coated ultrasmall Se particles (porous Se@SiO₂ nanospheres) to manage inflammatory osteolysis.

Results

Macrophage membrane-coated porous Se@SiO₂ nanospheres(M-Se@SiO₂) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO₂ reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments.

Conclusion

Our findings suggest that M-Se@SiO₂ have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO₂ are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty.

SUBMITTER: Ding C

PROVIDER: S-EPMC8607681 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Macrophage-biomimetic porous Se@SiO<sub>2</sub> nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

Ding Cheng C Yang Chuang C Cheng Tao T Wang Xingyan X Wang Qiaojie Q He Renke R Sang Shang S Zhu Kechao K Xu Dongdong D Wang Jiaxing J Liu Xijian X Zhang Xianlong X

Journal of nanobiotechnology 20211122 1

<h4>Background</h4>Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO<sub>2</sub>-coated ultrasmall Se particles (porous Se@Si ...[more]

PMID: 34809618

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Project description:BackgroundLipid peroxidation is a characteristic metabolic manifestation of diabetic retinopathy (DR) that causes inflammation, eventually leading to severe retinal vascular abnormalities. Selenium (Se) can directly or indirectly scavenge intracellular free radicals. Due to the narrow distinction between Se's effective and toxic doses, porous Se@SiO2 nanospheres have been developed to control the release of Se. They exert strong antioxidant and anti-inflammatory effects.MethodsThe effect of anti-lipid peroxidation and anti-inflammatory effects of porous Se@SiO2 nanospheres on diabetic mice were assessed by detecting the level of Malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), decreased reduced/oxidized glutathione (GSH/GSSG) ratio, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL) -1β of the retina. To further examine the protective effect of porous Se@SiO2 nanospheres on the retinal vasculopathy of diabetic mice, retinal acellular capillary, the expression of tight junction proteins, and blood-retinal barrier destruction was observed. Finally, we validated the GPX4 as the target of porous Se@SiO2 nanospheres via decreased expression of GPX4 and detected the level of MDA, GSH/GSSG, TNF-α, IFN-γ, IL -1β, wound healing assay, and tube formation in high glucose (HG) cultured Human retinal microvascular endothelial cells (HRMECs).ResultsThe porous Se@SiO2 nanospheres reduced the level of MDA, TNF-α, IFN-γ, and IL -1β, while increasing the level of GPX4 and GSH/GSSG in diabetic mice. Therefore, porous Se@SiO2 nanospheres reduced the number of retinal acellular capillaries, depletion of tight junction proteins, and vascular leakage in diabetic mice. Further, we identified GPX4 as the target of porous Se@SiO2 nanospheres as GPX4 inhibition reduced the repression effect of anti-lipid peroxidation, anti-inflammatory, and protective effects of endothelial cell dysfunction of porous Se@SiO2 nanospheres in HG-cultured HRMECs.ConclusionPorous Se@SiO2 nanospheres effectively attenuated retinal vasculopathy in diabetic mice via inhibiting excess lipid peroxidation and inflammation by target GPX4, suggesting their potential as therapeutic agents for DR.

Project description:Photodynamic-induced immunotherapy (PDI) is often hampered by low reactive oxygen species (ROS) yield, intra-tumor hypoxia, high glutathione (GSH) concentration, and immunosuppressive microenvironment. In view of this, a ruthenium (Ru)-based nanobattery (termed as IRD) with cascade-charged oxygen (O2), ROS, and photodynamic-induced immunotherapy by coordination-driven self-assembly of transition-metal Ru, photosensitizer indocyanine green (ICG), and organic ligand dithiobispropionic acid (DTPA). Then, IRD is camouflaged with macrophage membranes to obtain a nanobattery (termed as IRD@M) with targeting and immune evasion capabilities. Upon intravenous administration, IRD@M with a core-shell structure, nano diameter, and good stability can specifically hoard in tumor location and internalize into tumor cells. Upon disassembly triggered by GSH, the released Ru³⁺ not only catalyzes the conversion of endogenous hydrogen peroxide (H₂O₂) into O₂ to alleviate tumor hypoxia and reduce the expression of hypoxia-inducible factor-1α (HIF-1α), but also generates hydroxyl radicals (·OH) to elevate intracellular ROS levels. This process significantly enhances the photodynamic therapy (PDT) efficacy of the released ICG. Meanwhile, the released DTPA can significantly downregulate overexpressed GSH to reduce the elimination of ROS deriving from PDT by the exchange reaction of thiol-disulfide bond. It is also found that alleviating the hypoxic tumor microenvironment synergistically enhances the PDT efficacy, which in turn cascades to recharge the subsequent immune response, significantly improving the immunosuppressive tumor microenvironment and activating systemic tumor-specific immunity. Notably, in vitro and in vivo experimental results jointly confirm that such cascade-recharged macrophage-biomimetic Ru-based nanobattery IRD@M can achieve an obvious tumor elimination while results in a minimized side effect. Taken together, this work highlights a promising strategy for simple, flexible, and effective Ru-based immunogenic cell death (ICD) agents within PDI.

Dataset Information

Macrophage-biomimetic porous Se@SiO₂ nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

Background

Results

Conclusion

Publications

Macrophage-biomimetic porous Se@SiO<sub>2</sub> nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Macrophage-biomimetic porous Se@SiO2 nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

Background

Results

Conclusion

Publications

Macrophage-biomimetic porous Se@SiO<sub>2</sub> nanocomposites for dual modal immunotherapy against inflammatory osteolysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Macrophage-biomimetic porous Se@SiO₂ nanocomposites for dual modal immunotherapy against inflammatory osteolysis.