Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Wang Hongbo,Li Jing,Jin Jianbo,Hu Jingbo,Yang Chunlin
Oxidative stress plays a key role in the progress of acute lung injury (ALI), which is an acute, progressive respiratory failure characterized by alveolar capillary injury caused by various external and internal factors other than cardiogenic factors. Pulmonary vascular endothelial cells are the main target cells during ALI, and therefore the mitochondrial targeting antioxidant derivative triphenylphosphine-melatonin (TPP-MLT) was encapsulated in VCAM-1 antibodies-conjugated nanostructured lipid carriers (VCAM@TPP-MLT NLCs) for lung targeting delivery. VCAM@TPP-MLT NLCs could be preferentially internalized by inflammatory endothelial cells in lung tissues, and then the released TPP-MLT from NLCs effectively eliminated the excessive reactive oxide species (ROS) and ameliorated cell apoptosis. Overall, the results suggested that VCAM@TPP-MLT NLCs exhibited remarkable in vitro and in vivo therapeutic effect on ALI, and could be a promising and efficient strategy for the treatment of ALI.
研究领域:
药理学
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呼吸医学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nano Today
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2023
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IF 17.4
Honghui Wu,Xinchi Jiang,Yaosheng Li,Yunfei Dong,Juanjuan Zheng,Lu Li,Ying Li,Jinqiang Wang,Xianming Lin,Xiangnan Zhang,Tianyuan Zhang,Zhen Gu,Jianqing Gao
Blood-brain barrier (BBB) dis-integrity, a characteristic of extensive inflammatory encephalopathy, provides the access for brain-targeted drug delivery. Inspired from the bioresponsiveness of stem cell, we conceived of new nano-scale delivery strategy via neural stem cell membrane-derived bioresponsive vesicles (NSC-Lipo) for inflamed BBB target delivery. After recombination of neural stem cell membranes with simple liposomes , the functional ligands, especially very late antigen-4 (VLA-4), were entirely engrafted into NSC-Lipo and equipped the NSC-Lipo with “pass order” to the “selective gate”. It bestowed the bioresponsive vesicles with selective target the injured brain microvessel endothelial cells (BMECs) and penetrate into the lesion through the vascular cell adhesion molecule-1 (VCAM-1)/VLA-4 interaction in the post-ischemic mice model. The released anti-inflammatory agent, metformin , could reverse the inflammatory response of BMECs and rapidly recovers BBB’s integrity. With the repair of BBB’s integrity and down regulation of VCAM-1 expression, the targeting ability of bioresponsive vesicles cease to be in force as well. The bioresponsive vesicles led to enhanced survival rate of ischemic stroke mice (from 30 % to 90 %) after just a single injection compared to metformin loaded bare liposomes.
研究领域:
神经科学
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药剂学
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干细胞生物学
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药物递送系统
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产品关联
DOI
高影响因子
Journal of Pharmaceutical Analysis
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2023
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IF 8.8
Si-Yu Gui,Xin-Chen Wang,Zhi-Hao Huang,Mei-Mei Li,Jia-Hao Wang,Si-Yin Gui,Gan-Hua Zhang,Yao Lu,Li-Ming Tao,Hai-Sheng Qian,Zheng-Xuan Jiang
Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of VCAM-1, HIF-1α, and VEGF, causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H 2 O 2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.
研究领域:
药学
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纳米技术
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眼科学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Mengying Hou,Xuejie Wu,Ziyin Zhao,Qiurong Deng,Yongbing Chen,Lichen Yin
Neutrophils serve as a key contributor to the pathophysiology of myocardial ischemia reperfusion injury (MIRI), because the unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium to cause tissue damage. Herein, endothelial cell-targeting and reactive oxygen species (ROS)-ultrasensitive nanocomplexes (NCs) were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM), which cooperatively inhibited neutrophil recruitment by impeding neutrophil migration and adhesion. RPPT was first synthesized via crosslinking of PEI 600 with ditellurium followed by modification with PEG and the endothelial cell-targeting peptide cRGD. RPPT was allowed to envelope the DXM-loaded PLGA nanoparticles and condense the siVCAM-1. After systemic administration in rats experiencing MIRI, the cRGD-modified NCs efficiently targeted and entered the inflamed endothelial cells, wherein RPPT was sensitively degraded by over-produced ROS to trigger intracellular siVCAM-1 release and potentiate the VCAM-1 silencing efficiency. As a consequence of the complementary function of DXM and siVCAM-1, the NCs notably mitigated neutrophil infiltration into ischemic myocardium, provoking potent anti-inflammatory efficacy to reduce MIRI and recover cardiac function. The present study offers an effective approach for the controlled co-delivery of siRNA and drug cargoes, and it also highlights the importance of multi-dimensional manipulation of neutrophils in anti-inflammatory treatment. Statement of significance The unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium after myocardial ischemia reperfusion injury (MIRI). Here, endothelial cell-targeting and ROS-ultrasensitive nanocomplexes (NCs), comprised of PLGA NPs decorated with cRGD-poly(ethylene glycol) (PEG)-modified, ditellurium-crosslinked PEI (RPPT), were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM). DXM and siVCAM-1 with complementary functions inhibited both the migration and adhesion of neutrophils, efficiently interventing the neutrophil recruitment and interrupting the self-amplified inflammation cascade in the injured myocardium. The molecular design of RPPT renders an effective example for constructing polymeric materials with high ROS sensitivity, and it resolves the critical dilemma related to polycation-mediated siRNA delivery, such as siRNA encapsulation versus release, and transfection efficiency versus toxicity.
研究领域:
药学
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纳米技术
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心血管研究
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分子生物学
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炎症
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Jiulong Zhang,Xiaoyan Sun,Mengdan Xu,Xiufeng Zhao,Chunrong Yang,Kexin Li,Fan Zhao,Haiyang Hu,Mingxi Qiao,Dawei Chen,Xiuli Zhao
Circumventing immune resistance and boosting immune response is the ultimate goal of cancer immunotherapy . Herein, we reported a tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle for specifically inducing immunogenic cell death (ICD) in combination with TAM depletion. A versatile ROS-cleavable camptothecin (CPT) prodrug (DCC) was synthesized through a thioacetal linker between CPT and the ROS generator cinnamaldehyde (CA), which could self-assemble into a uniform prodrug nanoparticle to realize a positive feedback loop of “ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation.” This DCC was further modified with the TAM membrane (abbreviated as DCC@M2), which could not only target both primary tumors and lung metastasis nodules through VCAM-1/α 4 β 1 integrin interaction but also absorb CSF-1 secreted by tumor cells to disturb the interaction between TAMs and cancer cells. Our nanodecoy could effectively induce ICD cascade and deplete TAMs for priming tumor-specific effector T cell infiltration for antitumor immune response activation, which represents a versatile approach for cancer immunotherapy. Statement of significance A tumor-associated macrophage (TAM) membrane-camouflaged nanodecoy containing a self-amplifying reactive oxygen species (ROS)-sensitive prodrug nanoparticle was fabricated for the first time. This ROS-cleavable camptothecin (CPT)/cinnamaldehyde (CA) prodrug (DCC) could self-assemble into a uniform nanoparticle to realize the positive feedback loop of “ROS-triggered CA/CPT release and CA/CPT-mediated ROS generation.” After TAM membrane coating, this system (DCC@M2) could not only target both primary tumors and lung metastatic nodules but also scavenge CSF-1 secreted by tumor cells for TAM depletion for sufficient chemotherapy-sensitized immunotherapy.
研究领域:
癌症免疫治疗
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纳米医学
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药学
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免疫学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
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IF 4.527
Yang Wu,Yan Li,Liangqing Zheng,Pengcheng Wang,Yan liu,Yongning Wu,ZhiYong Gong
Nε-(carboxymethyl)lysine (CML) is a potentially noxious compound that is causing widespread concern due to its use in various food products. In this study, we investigated CML neurotoxicity via an in vivo experiment with mice, and an in vitro experiment using a 3D microvascular network model (with human brain vascular endothelial cell and human astrocyte) that simulated the blood-brain barrier. We found that CML could induce cell survival status variations, and histopathological changes to the brain. In addition, CML increased levels of oxidative stress , prompted the protein expression of the receptor for advanced glycation end-products (RAGE). CML up-regulated both the gene expression of RAGE, the activating protein-1 (AP-1), the inflammatory cytokines Interleukin-6 (IL-6), vascular cell adhesion molecule1 (VCAM-1), monocyte chemotactic protein1 (MCP-1). We, therefore, postulated that CML has the potential to deleteriously affect the nervous system through oxidative stress and that activation of the p38 MAPK-AP-1 signaling pathway might be implicated in this pathological process.
研究领域:
神经科学
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毒理学
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细胞生物学
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食品科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Di Wu,Tiancheng Gong,Zhongxiang Sun,Xihao Yao,Dongzhi Wang,Qiyang Chen,Qingsong Guo,Xiaohong Li,Yibing Guo,Yuhua Lu
The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is characterized by deposition of desmoplastic matrix (including collagen and hyaluronic acid). And the interactions between tumor-associated macrophages (TAMs) and tumor cells play a crucial role in progression of PDAC. Hence, the appropriate model of tumor cell-macrophage interaction within the unique PDAC TME is of significantly important. To this end, a 3D tumor niche based on dual-crosslinking gelatin methacrylate and hyaluronic acid methacrylate hydrogels was constructed to simulate the desmoplastic tumor matrix with matching compressive modulus and composition. The bionic 3D tumor niche creates an immunosuppressive microenvironment characterized by the downregulation of M1 markers and upregulation of M2 markers in TAMs. Mechanistically, RNA-seq analysis revealed that the PI3K-AKT signaling pathway might modulate the phenotypic balance and recruitment of macrophages through regulating SELE and VCAM-1. Furthermore, GO and GSEA revealed the biological process of leukocyte migration and the activation of cytokine-associated signaling were involved. Finally, the 3D tumor-macrophage niches with three different ratios were fabricated which displayed increased M2-like polarization and stemness. The utilization of the 3D tumor niche has the potential to provide a more accurate investigation of the interplay between PDAC tumor cells and macrophages within an in vivo setting.
研究领域:
癌症生物学
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组织工程
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生物材料
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免疫学
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细胞信号传导
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2021
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IF 7.963
Cuiyuan Jin,You Weng,Yi Zhang,Zhiwei Bao,Guiling Yang,Zhengwei Fu,Yuanxiang Jin
Propamocarb is a systemic carbamate fungicide used to fight diseases. The effect of propamocarb on the formation of atherosclerosis was evaluated in wild-type (WT) and ApoE knockout (ApoE −/− ) mice. C57BL/6 J WT mice were fed control diet or high-fat diet (HFD) with 20 mg/L propamocarb in drinking water for 24 weeks. Propamocarb significantly increased the serum levels of triglyceride, cholesterol and low-density lipoprotein cholesterol while decreasing high-density lipoprotein cholesterol. Simultaneously, propamocarb facilitated lipid accumulation in the liver and increased the expression of cholesterol synthesis and transport genes in the liver and ileum. Lipid accumulation was observed in the aortic roots of the propamocarb-treated mice fed HFD, and similar results were also observed with whole aorta staining. In addition, propamocarb exposure significantly increased the mRNA levels of IL-1β , TNF-α , ICAM-1 , and VCAM-1 in the aorta and the serum IL-1β, IL-6, and TNF-α levels in HFD groups treated with propamocarb. In ApoE −/− mice, the results were consistent with those obtained in WT mice after exposure to 20 mg/L propamocarb for 10 weeks. Meanwhile, propamocarb significantly increased the levels of CD36, NF-κB, VCAM-1 and ICAM-1 proteins in the aortas of ApoE −/− mice. Propamocarb further disrupted cholesterol metabolism and enhanced atherosclerosis and inflammatory responses much more substantially, indicating that propamocarb has the potential to accelerate the formation of atherosclerosis. An analysis of gut microbiota revealed that propamocarb altered the composition of gut microbiota in both WT and ApoE −/− mice. Interestingly, propamocarb increased the abundance of Peptostreptococcaceae, Ruminococcaceae, and Clostridiales_VadinBB60_group , which are related to atherosclerosis at the family level. The abundance of Paeniclostridium, Allobaculum, and Clostridioides , which are closely related to atherosclerosis, was also increased by propamocarb exposure. Our findings indicate that propamocarb exposure may promote atherosclerosis by disrupting lipid metabolism, increasing the inflammatory response, and altering the structure of gut microbiota.
研究领域:
药理学
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心血管疾病
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免疫学
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微生物学
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代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）