International Journal of Nanomedicine
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2020
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IF 5.115
Lingling Ou,Haiyingjie Lin,Yuwei Song,Guoqiang Tan,Xiujuan Gui,Jinyuan Li,Xiaoting Chen,Zhendong Deng,Shaoqiang Lin
Background Gene therapy is considered a novel way to treat osteosarcoma, and microRNAs are potential therapeutic targets for osteosarcoma. miR-214 has been found to promote osteosarcoma aggression and metastasis. Graphene oxide (GO) is widely used for gene delivery for the distinct physiochemical properties and minimal cytotoxicity. Methods Polyethyleneimine (PEI)-functionalized GO complex was well-prepared and loaded with miR-214 inhibitor at different concentrations. The load efficacy was tested by gel retardation assay and the cy3-labeled fluorescence of cellular uptake. The experiments of wound healing, immunofluorescence staining, Western blot, qRT-PCR and immunohistochemical staining were performed to measure the inhibitory effect of the miR-214 inhibitor systematically released from the complexes against MG63, U2OS cells and xenograft tumors. Results The systematic mechanistic elucidation of the efficient delivery of the miR-214 inhibitor by GO-PEI indicated that the inhibition of cellular miR-214 caused a decrease in osteosarcoma cell invasion and migration and an increase in apoptosis by targeting phosphatase and tensin homolog (PTEN). The synergistic combination of the GO-PEI-miR-214 inhibitor and CDDP chemotherapy showed significant cell death. In a xenograft mouse model, the GO-PEI-miR-214 inhibitor significantly inhibited tumor volume growth. Conclusion This study indicates the potential of functionalized GO-PEI as a vehicle for miRNA inhibitor delivery to treat osteosarcoma with low toxicity and miR-214 can be a good target for osteosarcoma therapy.
研究领域:
肿瘤学
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分子生物学
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纳米技术
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药学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Xin Sun,Chunyan Yang,Wei Liu,Ke Lu,Hao Yin
Graphene oxide (GO) is a biocompatible nanomaterial that has an inhibitory effect on insulin amyloid fibrillation. In order to enhance the inhibitory effect of GO and explore the rules of electrostatic interactions on the inhibitory effect, carboxyl group, PEI and PEG were coupled to the GO nanoplatelet surface to prepare inhibitors of different surface electrical properties. The effects of surface electrical properties of inhibitors on insulin fibrillation were investigated. The results showed that GO, carboxyl group modified GO (GO-COOH), PEI modified GO (GO-PEI), and PEG modified GO (GO-PEG) inhibited insulin fibrillation in a dose-dependent manner. Compared with GO, positive charge-modified GO-PEI and negative charge-modified GO-COOH enhanced the inhibitory effect, while uncharged polymer-modified GO-PEG weakened the inhibitory effect. The inhibitory effect of the inhibitors increased with the increase of surface charge density. The difference in inhibitory effect between GO-PEI and GO-COOH was due to the different electrostatic interactions between inhibitors and insulin, and the different inhibition mechanisms. In addition, inhibitors mainly interact with insulin during the nucleation phase to hinder insulin fibrillation. The charge modifications of graphene oxide enhanced the inhibitory effect on insulin fibrillation based on electrostatic interactions, which will provide new thoughts for the development of anti-amyloid fibrillation drugs.
研究领域:
纳米技术
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生物物理学
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材料科学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
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2018
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IF 3.226
Yajie Wang,Qiang Wang,Xiaoping Song,Jingjing Cai
Development of appropriate support for enzyme immobilization with approving loading capacity, stability and recyclable performance is a significant topic in enzyme chemistry . In this study, the hydrophilic polyethylenimine (PEI) modified magnetic graphene oxide (GO) composite (Fe 3 O 4 @ [email protected] ) was fabricated and acted as an efficient solid support for the immobilization of dextranase to improve the stability and recyclable performance. The GO nanosheet component not only provided abundant binding sites for decorating PEI molecules and further increasing the loading capacity of immobilized dextranase, but also acted as a soft matrix for enhancing the stability of immobilized dextranase. In addition, in combination of the unique magnetic separation property, the recyclable ability of immobilized dextranase was further improved. The loading amount of immobilized dextranase on as-developed Fe 3 O 4 @ [email protected] was determined to be 305.1 mg g −1 , which was 1.61 times that on the Fe 3 O 4 @PDA-PEI without GO component. Moreover, the as-developed Fe 3 O 4 @ [email protected] exhibited high immobilization efficiency (76.27%) and enzymatic activity (83.67%), improved stabilities in wide temperature conditions and pH solutions, and excellent reusability (85.78% of its initial activity after 20 cycles). These experimental results suggest that the immobilized dextranase is promising for various applications in biocatalytic engineering fields.
研究领域:
酶化学
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生物催化
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Theranostics
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2019
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IF 8.063
Lingling Ou,Yong Lan,Zhiqiang Feng,Longbao Feng,Junjie Yang,Yu Liu,Liming Bian,Jiali Tan,Renfa Lai,Rui Guo
Evidence indicates that microRNAs (miRNAs) play vital roles in regulating osteogenic differentiation and bone formation. Methods : Here, we show that a polyethyleneimine (PEI)-functionalized graphene oxide (GO) complex efficiently loaded with the miR-214 inhibitor is assembled into silk fibroin/hydroxyapatite (SF/HAP) scaffolds that spatially control the release of the miR-214 inhibitor. Results : SF/HAP/GO scaffolds with nanosized GO show high mechanical strength, and their hierarchical microporous structures promote cell adhesion and growth. The SF/HAP/GO-PEI scaffolds loaded with mir-214 inhibitor (SF/HAP/GPM) were tested for their ability to enhance osteogenic differentiation by inhibiting the expression of miR-214 while inversely increasing the expression of activating transcription factor 4 (ATF4) and activating the Akt and ERK1/2 signaling pathways in mouse osteoblastic cells (MC3T3-E1) in vitro . Similarly, the scaffolds activated the osteoblastic activity of endogenous osteoblast cells to repair critical-sized bone defects in rats without the need for loading osteoblast cells. Conclusion : This technology is used to increase osteogenic differentiation and mineralized bone formation in bone defects, which helps to achieve cell-free scaffold-based miRNA-inhibitor therapy for bone tissue engineering.
研究领域:
生物医学工程
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分子生物学
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组织工程
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骨科
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2021
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IF 15.881
Zhijie Zhang,Xiao Xiao,Yihao Zhou,Linjun Huang,Yanxin Wang,Qinglin Rong,Zhenyang Han,Huaijiao Qu,Zhijun Zhu,Shumao Xu,Jianguo Tang,Jun Chen
Tunable gating graphene oxide (GO) membranes with high water permeance and precise molecular separation remain highly desired in smart nanofiltration devices. Herein, bioinspired by the filtration function of the renal glomerulus, we report a smart and high-performance graphene oxide membrane constructed via introducing positively charged polyethylenimine-grafted GO (GO-PEI) to negatively charged GO nanosheets. It was found that the additional GO-PEI component changed the surface charge, improved the hydrophilicity, and enlarged the nanochannels. The glomerulus-inspired graphene oxide membrane (G-GOM) shows a water permeance up to 88.57 L m–2 h–1 bar–1, corresponding to a 4 times enhancement compared with that of a conventional GO membrane due to the enlarged confined nanochannels. Meanwhile, owing to the electrostatic interaction, it can selectively remove positively charged methylene blue at pH 12 and negatively charged methyl orange at pH 2, with a removal rate of over 96%. The high and cyclic water permeance and highly selective organic removal performance can be attributed to the synergic effect of controlled nanochannel size and tunable electrostatic interaction in responding to the environmental pH. This strategy provides insight into designing pH-responsive gating membranes with tunable selectivity, representing a great advancement in smart nanofiltration with a wide range of applications.
研究领域:
材料科学
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纳米技术
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环境工程
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化学工程
✓ 已验证
DOI
PubMed
高影响因子
APPLIED CLAY SCIENCE
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2022
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IF 5.907
Xiaohua Tian,Sujun Tian,Lulu Wang,Yanping Yang,Ruilong Zhang,Jiangdong Dai,Jianming Pan
The easy preparation of robust superwetting materials for oily wastewater disposal still remains a challenge. Inspired by the self-cleaning and mechanical properties of natural nacre underwater, herein, we have successfully developed sphere-rod quaternary artificial nacre-inspired meshes (named GO-PEI-SiO 2 -Hal) via interfacial self-assembly using 2D graphene oxide nanosheets , hyperbranched polyethyleneimine, SiO 2 nanospheres , and hollow halloysite nanotubes (Hal) as the building blocks. The nacre-like “brick-and-mortar” layered microstructure was successfully formed and tightly coated to the mesh, showing excellent mechanical properties with Young's modulus up to 19.7 ± 2.6 GPa. Compared to the ternary structures, the quaternary sphere-rod morphology improved the surface roughness , and these four organic/inorganic building blocks are all hydrophilic , which together resulted in the superhydrophilic and underwater superoleophobic characteristics. The effects of building block concentration, dipping number, and mesh size on wettability and oil-water separation performance were studied in detail. The optimal (GO-PEI-SiO 2 -Hal-1) 15 @Fe 300 mesh showed an underwater oil contact angle of 159 o for 1,2-dichloroethane, low oil adhesion, and excellent separation efficiency up to 99.8% at an ultrahigh flux up to 195,038 L m −2 h −1 . This nacre-like mesh exhibited excellent salt tolerance, acid-alkali resistance, recycling ability, and mechanical properties for practical oily wastewater treatment .
研究领域:
材料科学
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环境工程
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2020
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IF 5.115
Lingling Ou,Ting Sun,Minyi Liu,Ye Zhang,Zhiying Zhou,Xiaozhen Zhan,Lihong Lu,Qingtong Zhao,Renfa Lai,Longquan Shao
Background MicroRNAs (miRNAs) are widely believed to be promising targets for oral squamous cell carcinoma (OSCC) gene therapy. miR-214 has been identified as a promoter of OSCC aggression and metastasis. Methods Graphene oxide-polyethylenimine (GO-PEI) complexes were prepared and loaded with a miRNA inhibitor at different N/P ratios. The transfection efficiency of GO-PEI-inhibitor was tested in Cal27 and SCC9 cells. Moreover, the tumor inhibition ability of GO-PEI-inhibitor was measured in an OSCC xenograft mouse model by intratumoral injection. Results Here, we show that a GO-PEI complex efficiently delivers a miR-214 inhibitor into OSCC cells and controls the intracellular release of the miR-214 inhibitor. These results indicate that the GO-PEI-miR-214 inhibitor complex efficiently inhibited cellular miR-214, resulting in a decrease in OSCC cell invasion and migration and an increase in cell apoptosis by targeting PTEN and p53. In the xenograft mouse model, the GO-PEI-miR-214 inhibitor complex significantly prevented tumor volume growth. Conclusion This study indicates that functionalized GO-PEI with low toxicity has promising potential for miRNA delivery for the treatment of OSCC.
研究领域:
肿瘤学
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分子生物学
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基因治疗
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
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2022
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IF 0
Zhiwei Li,Jiaqi Bu,Xinyu Zhu,Hao Zhou,Kaiqun Ren,Paul K. Chu,Limin Li,Xiang Hu,Xiaofeng Ding
Programmed cell death receptor ligand 1 (PD-L1)/PD-1 signaling has been exploited to design inhibitors that deliver promising clinical outcome albeit with limited efficacy. Herein, we prepare graphene oxide (GO)-PEI-PEG with low cytotoxicity and long stability and GO-PEI-PEG delivers PD-L1 siRNAs to hepatocellular carcinoma (HCC) cells by the endocytosis-lysosome pathway. The functional GO-PEI-PEG/PD-L1 siRNAs decrease PD-L1 and PD-1 abundance, increase pro-inflammation cytokine IFN-γ and TNF-α release, and improve the proliferation activity of Jurkat T cells. Since GO-PEI-PEG targets the mouse liver effectively, the intrahepatic tumors in C57BL/6 mice are treated with GO-PEI-PEG/Pd-l1 siRNAs via the tail vein, resulting in shrinkage of the HCC tumors and boosting the anti-tumor efficacy in combination with oral sorafenib. A single treatment improves the total CD3 + and cytotoxic CD8 + T cell infiltration in the HCC tumor tissues and even spleen and upregulates the expression of Perforin, Gzmb, Ifng, Il-1b and Tnfa in the tumors after the combined treatment. Both the single and combined treatments enhance reactive oxygen species (ROS) accumulation, and improved HCC ferroptosis. The results suggest that GO-PEI-PEG delivered PD-L1 siRNAs combined with oral sorafenib can activate the adaptive immunity and tumor ferroptosis and reveal an effective therapy to treat advanced HCC patients.
研究领域:
肿瘤学
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分子生物学
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免疫学
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药理学
✓ 已验证
DOI
PubMed
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