Nanoscale
·
2018
·Vol. 10
·期 43
·20246-20255
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IF 7.233
Ri Ji,Xiaoyu Li,Chun Zhou,Qiwei Tian,Chang Li,Shujun Xia,Ronghui Wang,Yun Feng,Weiwei Zhan
Macrophage recruitment has emerged as the crucial force driving the initiation and progression of atherosclerotic lesions. Therefore, the identification of macrophages in plaques is of vital importance for identifying vulnerable plaques, and noninvasive imaging methods are particularly desirable. Some studies have reported that MRI can detect plaque macrophages through targeted nanoparticles, but it is still hard for an US to detect macrophages in atherosclerotic plaque. In this study, anti-CD68 receptor-targeted Fe-doped hollow silica nanoparticles (CD68-Fe-HSNs) were fabricated as a dual-modal US/MRI contrast agent for identifying macrophages of aorta ventralis atherosclerotic plaques in ApoE–/– mice, confirmed by immunofluorescence and bio-TEM. This system possesses biodegradable characteristics even though it is an inorganic mesoporous nanosystem, indicating its potential high biocompatibility for further in vivo research. We expect that these dual-modal US/MRI nanoparticles will play a role in assessing vulnerable plaque in future research studies.
研究领域:
生物医学工程
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分子影像学
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纳米技术
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心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
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2022
·
IF 6.14
Xue-Hui Shi,Jing-Ping Yuan,Ying-Ying Dai,Xing Liu,Shu-Lin Liu,Zhi-Gang Wang
In breast cancer (BC), the tumor microenvironment contains various cell types and extracellular components, of which CD68 and CD47 are two key factors. Recent studies have shown that simultaneous high expression of CD68 and CD47 is associated with poor prognosis in BC. However, there is no direct methodological evidence to support this finding. Here, using our own preparation of different functionalized quantum dots, we successfully achieved dual-color in situ fluorescence imaging of CD68 and CD47 with high spatial resolution. This imaging approach provided directly observable evidence that cancer cells evading immune responses are surrounded by more macrophages, suggesting that the coevolution of CD68 and CD47 during BC development can promote cancer cell metastasis. Taken together, our results provide direct evidence for evaluating prognostic factors of BC and will contribute to our understanding of the tumor microenvironment and its role in tumor evolution.
研究领域:
癌症生物学
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免疫学
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分子生物学
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医学影像
✓ 已验证
DOI
高影响因子
MOLECULAR CARCINOGENESIS
·
2019
·Vol. 58
·期 8
·1481-1491
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IF 3.411
Yuan-yuan Guo,Chen Xu,Yan Fang,Cai-e Wang,Na Gao,Qiang Wen,Hai-ling Qiao
Cytochrome P450 2E1 (CYP2E1) is an important drug-metabolizing enzyme that has been recognized as one of the risk factors for hepatofibrosis. Macrophages play key roles in regulating hepatofibrosis progression and resolution. However, whether CYP2E1 is involved in the regulation of macrophage polarization during hepatofibrosis is still unclear. Herein, we measured CYP2E1 activity and the expression of CD163 (an M2 marker) and CD68 (a pan-macrophage marker) in hepatofibrotic tissue from HCC patients (n = 26) with comparison to normal liver tissue (n = 26). The relationship of CYP2E1 activity in vivo and the CD163/CD68 ratio (an indicator of M2 polarization), as well as the extent of hepatofibrosis, were evaluated in diethylnitrosamine (DEN)-treated Sprague-Dawley rats. Strikingly, CYP2E1 activity and expression of CD68 increased and the CD163/CD68 ratio decreased, especially in hepatofibrotic tissue with higher CYP2E1 activity. Expression of α-SMA, Ki67, and PCNA were positively correlated with CYP2E1 activity and inversely correlated with the CD163/CD68 ratio. Furthermore, CYP2E1 activity showed an inverse correlation with the CD163/CD68 ratio. Overall, high CYP2E1 activity aggravates hepatofibrosis by restraining M2 macrophage polarization, providing a novel insight for understanding the profibrotic activity of CYP2E1 and a promising avenue for hepatofibrosis therapy.
研究领域:
肝病学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Yang Ding,Shengyun Wan,Long Ma,Kaikai Wei,Kun Ye
Hindlimb ischemia (HLI) is an arterial occlusive disease that exposes the patients to the risk of limb gangrene and loss. Polarization of macrophages is related to HLI-induced inflammation. Period circadian regulator 1 (PER1) is a core component of the circadian clock. We first showed, based upon bioinformatics analysis of microarray data, that PER1 expression was reduced in monocytes from patients with critical limb ischemia. The proximal femoral artery in the left hindlimb of male mice was ligated and then the femoral artery and its collateral branches were removed to establish the HLI mouse model. After modeling, a single intramuscular injection of 1 × 10 9 pfu Ad-PER1 was performed at the adductor and gastrocnemius muscles. The gastrocnemius muscle tissues were collected at day 0, 3, 7, 14, 21 post-HLI. There was obvious pathological necrosis, accompanied with reduced expression of PER1 in the muscle tissues of HLI mice. Expression of CD68 and CD31 seemed to be corresponded to PER1 in gastrocnemius muscle, implying the potential of PER1 in regulating macrophage-related inflammation and angiogenesis . PER1 overexpression diminished myocyte damage, promoted blood flow restoration and improved behavioral scores of HLI mice. Immunostaining of CD31 and α-SMA revealed that PER1 upregulation reversed HLI-induced decreases in capillary and arteriole density. In vitro, RAW264.7 cells were cultured in hypoxia (1% O 2 ) for 24 h. The percentage of pro-inflammatory CD86 + macrophages (M1 type) was decreased and that of anti-inflammatory CD206+ macrophages (M2 type) was increased when PER1 was overexpressed. Moreover, the expression levels of TNF-α, IL-6 and M1-type marker iNOS were decreased, and levels of IL-10 and M2-type marker Arg-1 were increased by PER1 in gastrocnemius muscle of HLI mice and hypoxia-treated RAW264.7 cells. PER1 might reduce M1 macrophage polarization and promote M2 macrophage polarization, and thus exert anti-inflammatory and pro-angiogenic actions. Our findings suggest that PER1 overexpression promotes functional recovery of mice with HLI through regulating macrophage polarization.
研究领域:
心脏病学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
·
IF 4.4
Xiaowen Fu,Gan Hu,Adil M. Abker,Deog-Hwan Oh,Meihu Ma,Xing Fu
Hydrogels have emerged as a promising option for treating local scald wounds due to their unique physical and chemical properties. This study aims to evaluate the efficacy of ovalbumin/gelatin composite hydrogels in repairing deep II-degree scald wounds using a mouse dorsal skin model. Trauma tissues collected at various time points are analyzed for total protein content, hydroxyproline content, histological features, and expression of relevant markers. The results reveal that the hydrogel accelerates the healing process of scalded wounds, which is 17.27% higher than the control group. The hydrogel treatment also effectively prevents wound enlargement and redness of the edges caused by infection during the initial stage of scalding. The total protein and hydroxyproline content of the treated wounds are significantly elevated. Additionally, the hydrogel up-regulates the expression of VEGF (a crucial angiogenic factor) and down-regulates CD68 (a macrophage marker). In summary, this study provides valuable insights into the potential of multifunctional protein-based hydrogels in wound healing.
研究领域:
生物医学工程
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伤口愈合
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材料科学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xin Xiao,Ailian Zhu,Gang He,Seiichi Tokula,YiTing Yang,Yang Qing,Yali Liu,HanWen Hu,Qin Song
A miscellaneous polysaccharide, PAP55–3-1, with a molecular weight of 23.03 kDa, was isolated from Periplaneta americana through extraction with dilute alkali solution, ethanol precipitation, and column chromatography purification. Structural analysis shows that PAP55–3-1 is mainly composed of five monosaccharides: galactosamine hydrochloride, glucosamine hydrochloride, galactose, glucose and mannose. Its main glycosidic bonds are: Manp-(1→, Galp-(1→, →3)-Galp-(1→, →3,6)-Manp-(1→, →2,6)-Manp-(1→, →6)-Manp-(1→, →4)-Galp-(1→, →6-Glcp-(1→, →6)-Galp-(1→, →2)-Manp-(1 →, →3,4)-Glcp-(1→, →3,6)-Galp-(1→. In vitro experiments demonstrated that PAP55–3-1 can effectively inhibit reactive oxygen species (ROS) and O 2 − production following H 2 O 2− induction. After H 2 O 2− induction, HIF-1α (hypoxia-inducible factor) was translocated in mitochondria PAP55–3-1 increased localization of HIF-1α was located on mitochondria to maintain the stability of mitochondrial function stability, thereby effectively inhibiting H 2 O 2 -induced mitochondrial oxidative damage. Additionally, PAP55–3-1 inhibited the M1 polarization of macrophages stimulated by H 2 O 2 and promoted the phenotype polarization of macrophages from M1 to M2, displaying anti-inflammatory and pro-repair properties. In vivo experimental results indicated that PAP55–3-1 promoted wound healing in mice. Immunohistochemical experiments revealed a reduction in CD68 expression and increase in CD206 expression in both positive and the high-dose polysaccharide group control group. This further demonstrated that PAP55–3-1 promotes the phenotype polarization of macrophages from M1 to M2, exerting anti-inflammatory and wound-healing activities.
研究领域:
免疫学
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药理学
·
生物化学
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细胞生物学
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伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Dan Mu,Xin Wang,Huiting Wang,Xuan Sun,Qing Dai,Pin Lv,Renyuan Liu,Yu Qi,Jun Xie,Biao Xu,Bing Zhang
Background Photodynamic therapy (PDT) has achieved continued success in the treatment of tumors, but its progress in the treatment of atherosclerosis has been limited, mainly due to the low tissue-penetration ability of the excitation light for photosensitizers.Methods In this study, we designed a chemiexcited system producing singlet oxygen in an attempt to apply PDT for the treatment of atherosclerosis without the irradiation of external light. The system designed was polymeric nanoparticles (NPs) equipped with chemical fuel and photosensitizers, cross-linked with an Fe3+–catechol complex for stabilization and magnetic resonance imaging (MRI).Results The system (FeCNPs for short) accumulated effectively in plaques, providing persistent and enhanced T1-weighted contrast ability. FeCNPs also prevented progression of atherosclerosis via macrophage elimination, and obviously reduced plaque size and thickness revealed by T1-weighted MRI. Expression of CD68, MCP1, and TNFα was significantly reduced after treatment. However, low doses of FeCNPs exhibited better therapeutic efficacy than high doses. Furthermore, low-dose FeCNPs exhibited effective macrophage elimination in aortic arches and abdominal aortae, but inefficiency in the thoracic aorta, aortic hiatus, and aorta–iliac bifurcation.Conclusion This study provides the first example of a combination of MRI and chemiexcited PDT for atherosclerosis, evidencing the effectiveness of PDT and providing significant pointers for developing nanotherapy on atherosclerosis.
研究领域:
纳米医学
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心血管疾病
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诊疗学
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医学影像
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药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Dan Su,Zhong Chen,Xiaobin An,Junkai Yang,Jinan Yang,Xuqiao Wang,Yang Qu,Chen Gong,Yani Chai,Xiaoying Liu,Wei Cheng,Dongyang Wang,Yan Wu,Jing Ma,Xinyue Zhao,Qin Wang,Yun Xu,Haisheng Peng,Jing Ai
The complex etiologies and mechanisms of Alzheimer's disease (AD) underscore the importance for devising multitarget drugs to achieve effective therapy. MicroRNAs (miRNAs) are capable of concurrently regulating the expression of multiple proteins by selectively targeting disease- associated genes in a sequence-specific fashion. Nonetheless, as RNA-based drugs, their stability in the circulation and capacity of traversing the blood–brain barrier (BBB) is largely compromised, thereby limiting their potential clinical applications. In this study, we formulated the nanoliposomes encapsulating polyethyleneimine (PEI)/ miR-195 complex (DPMT@PEI/ miR-195 ) that was engineered through dual modifications to contain P -aminophenyl-alpha-d-mannopyranoside (MAN) and cationic cell-penetrating peptide (TAT). DPMT@PEI/ miR-195 exhibited the enhanced BBB- and cell membrane penetrating capability. As expected, we observed that DPMT@PEI/ miR-195 administered through intravenous tail injection of produced greater effectiveness than donepezil and the same range of effect as aducanumab in alleviating the cognitive decline in 7-month-old APP/PS1 mice. Moreover, the combination treatment with DPMT@PEI/ miR-195 and donepezil effectively ameliorated the deterioration of cognition in 16-month-old APP/PS1 mice, with enhanced effects than either DPMT@PEI/ miR-195 or donepezil alone. Furthermore, DPMT@PEI/ miR-195 effectively attenuated the positive signals of Aβ, AT8, and CD68 in APP/PS1 mice without notable side effects. Our findings indicate DPMT@PEI/ miR-195 as a promising potentially new agent or approach for the prophylaxis and treatment of early and advanced stages of Alzheimer's disease.
研究领域:
神经科学
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药理学
·
分子生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Yujiao Liu,Shuning Chen,Jiangchuan Sun,Shenyin Zhu,Chunyan Chen,Wan Xie,Jiao Zheng,Yi Zhu,Linlin Xiao,Lan Hao,Zhigang Wang,Shufang Chang
We have successfully fabricated versatile folate-targeted and oxygen/indocyanine green-loaded lipid nanoparticles (FA-OINPs) for dual-mode imaging-guided therapy in ovarian cancer cells and subcutaneous xenograft models. FA-OINPs were demonstrated to have great potential as superb contrast agents to enhance ultrasound and photoacoustic (US/PA) imaging We have successfully fabricated versatile folate-targeted and oxygen/indocyanine green-loaded lipid nanoparticles (FA-OINPs) for dual-mode imaging-guided therapy in ovarian cancer cells and subcutaneous xenograft models. FA-OINPs were demonstrated to have great potential as superb contrast agents to enhance ultrasound and photoacoustic (US/PA) imaging in vitro and in vivo. Confocal laser scanning microscopy and flow cytometry analysis verified that FA-OINPs could specifically target SKOV3 ovarian cancer cells and be endocytosed with a remarkable efficiency. Compared with other therapeutic options, FA-OINPs exhibited an excellent therapeutic outcome after exposure to laser and ultrasound. The MTT assay and flow cytometry analysis confirmed that cytotoxicity effects and apoptosis/necrosis rates were significantly increased. The fluorescence microscopy and fluorescence microplate reader detection validated that the generation of intracellular reactive oxygen species (ROS) was dramatically improved. Immunohistochemical analyses of tumor tissues demonstrated the enhanced tumor apoptosis, the decreased vascular endothelial growth factor (VEGF) and microvascular density (MVD) expression, and the decreased expression of CD68 after treatment. The presented results suggest that photo-sonodynamic/photothermal mediated FA-OINPs could provide a promising strategy for synergistic therapy in ovarian cancer with the guidance of US/PA dual-mode imaging.
研究领域:
癌症研究
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纳米技术
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生物医学工程
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诊疗学
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成像科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Lin Zou,Yao Zhang,Nihad Cheraga,Oluwatosin David Abodunrin,Kai-Yun Qu,Li Qiao,Yu-Qing Ma,Li-Juan Chen,Ning-Ping Huang
Recently, photodynamic therapy (PDT) has been considered as a new strategy for atherosclerosis treatment. Targeted delivery of photosensitizer could significantly reduce its toxicity and enhance its phototherapeutic efficiency. CD68 is an antibody that can be conjugated to nano-drug delivery systems to actively target plaque sites, owing to its specific binding to CD68 receptors that are highly expressed on the surfaces of macrophage-derived foam cells. Liposomes are very popular nanocarriers due to their ability to encapsulate a wide range of therapeutic compounds including drugs, microRNAs and photosensitizers, and their ability to be surface-modified with targeting moieties leading to the development of nanocarriers with an improved targeted ability. Hence, we designed a Ce6-loaded liposomes using the film dispersion method, followed by the conjugation of CD68 antibody on the liposomal surface through a covalent crosslinking reaction, forming CD68-modified Ce6-loaded liposomes (CD68-Ce6-mediated liposomes). Flow cytometry results indicated that Ce6-containing liposomes were more effective in promoting intracellular uptake after laser irradiation. Furthermore, CD68-modified liposomes significantly strengthened the cellular recognization and thus internalization. Different cell lines have been incubated with the liposomes, and the results showed that CD68-Ce6-mediated liposomes had no significant cytotoxicity to coronary artery endothelial cells (HCAEC) under selected conditions. Interestingly, they promoted autophagy in foam cells through the increase in LC3-Ⅰ, LC3-Ⅱ expression and the decrease in p62 expression, and restrained the migration of mouse aortic vascular smooth muscle cells (MOVAS) in vitro. Moreover, the enhancement of atherosclerotic plaque stability and the reduction in the cholesterol content by CD68-Ce6-mediated liposomes were dependent on transient reactive oxygen species (ROS) generated under laser irradiation. In summary, we demonstrated that CD68-Ce6-mediated liposomes, as a photosensitizer nano-drug delivery system, have an inhibitory effect on MOVAS migration and a promotion of cholesterol efflux in foam cells, and thereby, represent promising nanocarriers for atherosclerosis photodynamic therapy.
研究领域:
药理学
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纳米技术
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心血管疾病
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Materials Technologies
·
2025
·
IF 6.2
Dandan Wei,Guanhua Jiao,Yinghua Tao,Liuxin Yang,Tao Liu,Fengya Jing,Tianzhu Zhang
Development of an antiadhesion polypropylene (PP) mesh in hernia repair is a recognized need because its efficacy is limited by severe abdominal adhesions. The porous structure of PP mesh can facilitate the integration between prosthetic material and abdominal tissue and promote the repair of abdominal wall defect. Herein, an antiadhesion composite hydrogel coating composed of polyvinyl alcohol (PVA) and hyaluronic acid methacrylate (HAMA) is fabricated on the surface of PP mesh through ultraviolet photopolymerization combined with freezing–thawing method. The resulted composite hydrogel coated PP mesh retain 43.33% of the pore structure by this way. In vitro tests proved the as-prepared PP mesh exhibit excellent hydrophilicity and biocompatibility. Meanwhile, the hydrogel coating shows good stability on the surface of PP mesh in phosphate buffered saline medium. After implantation in a rat abdominal wall defect model, the modified PP mesh effectively prevents the formation of adhesion by reducing inflammatory response and suppressing excessive deposition of collagen fiber. Immunohistochemical staining results demonstrate that the modified PP mesh can not only decrease the expression of IL-6, TNF-α, and CD68 but also promote the expression of CD31. Thus, this type of PP mesh with preventing postoperative adhesions and improving angiogenesis may be a promising clinical prosthetic material.
研究领域:
生物医学工程
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材料科学
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组织工程
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外科研究
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Cheng Peng,Shiqi Kang,Meijun Jiang,Mingxi Yang,Xu Gong
Background The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury.Materials and Methods RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury.Results In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased.Conclusion In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.
研究领域:
生物医学工程
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药学
·
组织工程
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骨科
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）