JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-16
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IF 10.435
Tan Qingqin,He Lingjie,Meng Xiaojun,Wang Wei,Pan Hudan,Yin Weiguo,Zhu Tianchuan,Huang Xi,Shan Hong
Background The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment.Results Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction.Conclusion Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.
研究领域:
药理学
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纳米技术
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免疫学
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病毒学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2024
·Vol. 15
·期 1
·1-17
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IF 14.7
Lin Lin,Ba Zhaojing,Tian Hao,Qin Haoxiang,Chen Xi,Zhou Xin,Zhao Shanlan,Li Lang,Xue Fangchao,Li Hong,He Lang,Li Xiaochen,Du Jiahui,Zhou Zhenhua,Zeng Wen
There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs’ long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.
研究领域:
生物医学工程
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诊疗学
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心血管医学
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神经学
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医学成像
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DOI
PubMed
高影响因子
Small
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2024
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IF 13
Rong Chen,Tingting Hu,Yu Lu,Shuqing Yang,Min Zhang,Chaoliang Tan,Ruizheng Liang,Yuji Wang
Photodynamic therapy (PDT) is demonstrated to be effective in inducing antitumor immune responses for tumor metastasis treatment. However, tumor hypoxia, inferior tissue penetration of light, and low singlet oxygen ( 1 O 2 ) quantum yield significantly hamper the efficacy of PDT, thus weakening its immune function. Moreover, PDT-mediated neutrophil extracellular traps (NETs) formation can further reduce the therapeutic effectiveness. Herein, the use of defect-rich CoMo-layered double hydroxide (DR-CoMo-LDH) nanosheets as a carrier to load a typical peptidyl arginine deiminase 4 inhibitor, i.e., YW4-03, to construct a multifunctional nanoagent (403@DR-LDH) for PDT/immunotherapy, is reported. Specifically, 403@DR-LDH inherits excellent 1 O 2 generation activity under 1550 nm laser irradiation and improves the half-life of YW4-03. Meanwhile, 403@DR-LDH plus 1550 nm laser irradiation can stimulate immunogenic cell death to promote the maturation of dendric cells and activation/infiltration of T cells and significantly downregulate H3cit protein expression to inhibit NETs formation, synergistically promoting the antitumor metastasis effect. Taken together, 403@DR-LDH can kill cancer cells and inhibit tumor growth/metastasis under 1550 nm laser irradiation. Single-cell analysis indicates that 403@DR-LDH can regulate the ratio of immune cells and immune-related proteins to improve the tumor immune microenvironment, showing strong efficacy to inhibit the tumor growth, metastasis, and recurrence.
研究领域:
癌症研究
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纳米技术
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免疫治疗
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光动力疗法
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肿瘤生物学
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2024
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IF 5.6
Xie Yinhong,Chi Mengchen,Yang Xinlei,Dong Ruichen,Yang Ao,Yin Antao,Weng Yajun
Modification of polylactic acid (PLA) is a promising strategy for the next generation of bioresorbable vascular stent biomaterials. With this focus, FeMOFs nanoparticles was incorporated in PLA, and then post loading of CO was performed by pressurization. It showed FeMOFs incorporation increased hydrophilicity of the surface and CO loading, and CO release was sustained at least for 3d. It is well acknowledged NETosis and macrophage mediated inflammation are the principal effectors of atherosclerosis and cardiovascular disease, and it further increases the risk of late stent thrombosis and restenosis. In this study, the effects of CO release of PLA/FeMOFs/CO on NETosis and macrophage behavior were thoroughly explored. In vitro evaluation results showed that PLA/FeMOFs/CO significantly inhibited neutrophil extracellular traps (NETs) release and neutrophil elastase (NE) expression by reducing intracellular ROS in a simulated inflammatory environment. It reduced LPS-induced macrophage inflammation with decreased TNF-α expression and increased IL-10 expression. Meanwhile it enhanced endothelial cell activity and growth in inflammatory environment, and inhibited platelet adhesion and activation. In vivo implantation results confirmed that PLA/FeMOFs/CO reduced the macrophages and neutrophils mediated inflammatory response, thus reduced the neointimal hyperplasia. Overall, PLA/FeMOFs/CO effectively prevented the inflammation and restenosis associated with PLA implantation. Our study provides a new strategy to improve the immunocompatibility of PLA implant materials.
研究领域:
生物材料
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心血管工程
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免疫学
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组织工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Jun Zhang,Lei Su,Zhinan Liu,Jincheng Tang,Lichen Zhang,Ziang Li,Dong Zhou,Zhuo Sun,Kun Xi,Peirong Lu,Guohua Deng
Following an ocular chemical injury, the release of neutrophil extracellular traps (NETs) triggers an innate immune cascade fibrotic effect involving macrophages (Mø), which limits corneal repair. However, the interplay and mechanisms between NETs and macrophages, as well as the coordination between the innate immunity and corneal repair, remain challenging issues. Using a co-culture system, we report that chemical stimulation exacerbates the accumulation of reactive oxygen species (ROS) within the polymorphonuclear neutrophils, leading to NET formation and the activation of M2 macrophages, ultimately inducing pathological fibrosis of the ocular surface through the IL-10/STAT3/TGF-β1/Smad2 axis. Inspired by the locally formed acidic microenvironment mediated by innate acute inflammatory stimulation, we further integrate sericin with oxidized chitosan nanoparticles loaded with black phosphorus quantum dots (BPQDs) using Schiff base chemistry to construct a functional pH-responsive hydrogel. Following corneal injury , the hydrogel selectively releases BPQDs in response to the acidic environment, inhibiting the innate immune cascade fibrosis triggered by the PMN-ROS-NETs. Thus, corneal pathological fibrosis is alleviated and reshaping of the ocular surface takes place. These results represent a refinement of the mechanism of inherent immune effector cell interactions, and provide new research ideas for the construction of nano biomaterials that regulate pathological fibrosis.
研究领域:
生物材料
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免疫学
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眼科
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组织工程
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纳米技术
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DOI
PubMed
高影响因子
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