ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2022
·Vol. 414
·期 5
·1881-1890
·
IF 4.478
Wu Yike,Liu Yuanyuan,Shang Zhengjun,Liu Xin,Xu Yong,Liu Wenlan
Aberrant protein N-glycosylation is one of the hallmarks of malignancy, while its role in oral cancer (OC) progression is still poorly understood making it a perfect biomarker for early-stage cancer. In this work, we describe a MALDI-MS-based N-glycomic analysis with multivariate data analysis approach for exploration and classification of the patients with OC. Various statistical analyses were used to determine differential N-glycome profiles. There were 8 glycan structures significantly increased ( p < 0.05) in all OC-derived microvesicles (MVs). Importantly, the increases in these glycans were significantly greater in the early stage of OC than those in the advanced stage of OC. Additionally, N-glycomic profiles from the serum were also performed, demonstrating a significant change of 11 glycan structures ( p < 0.05). Our data highlighted the effectiveness approach of MALDI-MS-based MV N-glycomic profiling on OC screening, and presented strong potential for further identifying targeted glycoproteomics signatures of the cancer.
研究领域:
生物化学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2025
·
IF 3.8
Xiaotian Wan,Xiyu Liu,Pan Wu,Yongmei Li,Yuanyuan Shi,Yueli Nie,Keyong Zhang,Ze Jin,Ruiyun Song,Zhikun Zhang,Lu Gan,Jian He
Objective Exploring the role and mechanism of a novel bioorthogonal system using transition metals as catalysts in the treatment of hepatocellular carcinoma (HCC). Methods Initially, a catalytic ruthenium (Ru) complex and the substrate alloc-RH 110 were synthesized, followed by the identification of their structures utilizing mass spectrometry and nuclear magnetic resonance (NMR) techniques. The catalytic efficacy of the Ru complex was then assessed using a fluorescence spectrophotometer. Subsequently, employing HepG2 cells as the cellular source, cell-derived vesicles encapsulating the Ru complexes, designated as EVs@Ru, were prepared. The EVs@Ru were characterized by measuring their particle size and Zeta potential, observing morphological features under transmission electron microscopy (TEM), and detecting specific protein expressions via Western blot analysis. Drug loading within the EVs@Ru was quantified using inductively coupled plasma mass spectrometry (ICP-MS), and their catalytic efficiency was evaluated. In vitro, the low-activity prodrug alloc-DOX was synthesized and its toxicity, along with the drug concentration in EVs@Ru, was determined. Further, the catalytic cytotoxicity of alloc-DOX against HepG2 cells encapsulated in EVs@Ru was analyzed through microscopic observation, CCK-8 assays, and apoptosis experiments. For in vivo studies, a tumor-bearing mouse model was established using human liver cancer HepG2 cells to observe the antitumor effects. Finally, the primary organs of each group of tumor-bearing mice were assessed for in vivo safety. Results ESI-MS and 1H NMR confirmed the accurate structure of Ru complexes and alloc-RH 110. The Ru complexes achieved full catalytic conversion of alloc-RH 110 within 24 hours. EVs and EVs@Ru exhibited particle sizes of ∼116.85 nm and ∼281.88 nm, respectively, with Zeta potentials of ∼-20.86 mV and ∼-25.89 mV, both appearing quasi-circular under TEM. WB analysis verified the presence of vesicle-specific marker proteins in both, confirming their cell-derived nature. ICP-MS determined a drug loading of 21.90 μg/mL for EVs@Ru, with an encapsulation efficiency of ∼24.86%. Fluorescence spectrophotometry demonstrated 100% catalytic efficiency for EVs@Ru. Synthetic alloc-DOX validated by 1H NMR and ESI-MS matched literature data. MTT and CCK-8 assays confirmed low toxicity for alloc-DOX and Ru complexes, setting the experimental drug concentration at 4μM. In vitro, the EVs@Ru+alloc-DOX group exhibited potent HepG2 cell killing and apoptosis. In vivo, this group significantly inhibited tumor growth in tumor-bearing mice, with no observed toxicity to vital organs, indicating good biosafety. Conclusion The integration of bio-derived microvesicles (MVs) with transition metal catalysts has resulted in a biologically orthogonal system for efficient Ru complex delivery to tumor sites. This system facilitates controlled release of the Ru complexes, enabling tumor cell elimination. This innovative strategy holds great promise for enhancing tumor immunity and targeted therapeutic approaches.
研究领域:
肿瘤学
·
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2016
·
IF 1.405
De-jing Wang,Chen-meiyi Wang,Yi-ting Wang,Hai Qiao,Liao-qiong Fang,Zhi-biao Wang
Background The complex process by which lactation is initiated upon neonate delivery remains incompletely understood. Microvesicles (MVs) can transmit microRNAs (miRNAs) into recipient cells to influence cell function, and recent studies have identified miRNAs essential for mammary gland development and lactation. This study aimed to investigate the expression of lactation-related miRNAs in MVs isolated from human umbilical cord blood immediately after delivery. Material/Methods Umbilical cord blood samples were collected from 70 healthy pregnant women, and MVs were isolated through differential centrifugation and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were screened using bioinformatics tools for miRNA target prediction, gene ontology, and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression analysis, and the results were validated by real-time PCR. Upon exposure of HBL-100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence confocal microscopy and β-casein secretion was detected by ELISA. Results Spherical MVs extracted from umbilical cord blood expressed CD63 and had an average diameter of 167.0±77.1 nm. We profiled 337 miRNAs in human umbilical cord blood MVs and found that 85 were related to lactation by bioinformatics analysis. The 25 most differentially expressed lactation-related miRNAs were validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture, and significantly increased secretion of β-casein was observed after 96 h from cells exposed to MVs (P<0.05). Conclusions Umbilical cord blood MVs contain many lactation-related miRNAs and can induce β-casein production by HBL-100 cells in vitro . Thus, umbilical cord blood MVs may mediate secretion of β-casein through miRNAs, thereby playing an important role in fetal-maternal crosstalk.
研究领域:
妇产科学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2021
·Vol. 39
·期 7
·856-864
·
IF 3.603
Wang Jing-Hong,Chen Rui,Zhao Zi-Qing,Shen Jie,Yang He,Luo Yan,Chen Gao-Jian,Chen Hong,Brash John L.
Herein we present a new perspective showing that water-soluble liquids, when added to water, undergo transient emulsification before complete dissolution. Thus, non-amphiphilic macromolecules can self-assemble at the two-miscible-phase interface when cononsolvent effect appears. A representative case shown here is that when poly( N -isopropylacrylamide) (PNIPAm), prepared by aqueous radical polymerization, in methanol solution is added into water, the polymer chains rapidly self-assemble into hollow micro-vesicles based on the cononsolvency at water/methanol interface. This finding provides a subtle strategy to prepare hollow micro-vesicles by non-amphiphilic polymers without template participating. We proposed a new concept “interfacial cononsolvency” to describe the formation process. Due to the easy modification process, sugar-contained PNIPAm chains are synthesized by copolymerization. As an application example, it is shown that these sugar-contained PNIPAm chains can afford “sweet” micro-vesicles (containing glucose residues). And the “sweet” micro-vesicles can well mimick the protocells which are involved in the recognition of bacteria.
研究领域:
材料科学
·
纳米技术
·
高分子化学
·
胶体科学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2025
·
IF 14.1
Zixuan Dong,Xiaobing Liu,Shichun Li,Xiaoling Fu
The aberrant cellular senescence in chronic wounds presents a significant barrier to healing. Mitochondrial dysfunction is critical in initiating and maintaining cellular senescence, underscoring therapeutic potential in restoring mitochondrial function by delivering healthy mitochondria to wound cells. However, approaches for delivering mitochondria to achieve optimized wound repair remain lacking. Herein, enucleated MSCs-derived microvesicles containing functional mitochondria (Mito@euMVs) via simple extrusion are developed. By controlling the size of microvesicles within a small micron-scale range, the mitochondrial encapsulation efficiency is optimized. Mito@euMVs effectively delivered mitochondria into fibroblasts and HUVECs, inhibiting and rejuvenating hyperglycemia-induced cellular senescence. To enhance the clinical applicability, soluble PVA microneedle patches for the transdermal Mito@euMVs delivery are utilized. In diabetic rats with pressure sores, the senescence-inhibiting and -rescuing properties of Mito@euMVs are further validated, along with their therapeutic efficacy, demonstrating their potential for chronic wound repair. Moreover, as a versatile delivery vehicle for mitochondria, Mito@euMVs hold promising for treating mitochondrial dysfunction and aging-related conditions.
研究领域:
医学
·
细胞生物学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Lingkai Dong,Minchao Liu,Meng Fang,Qianqian Lu,Xingjin Li,Yanming Ma,Tiancong Zhao
Albeit microemulsion systems have emerged as efficient platforms for fabricating tunable nano/microstructures, lack of understanding on the emulsion-interfacial assembly hindered the control of fabrication. Herein, a nucleation-inhibited microemulsion interfacial assembly method is proposed, which deviates from conventional interfacial nucleation approaches, for the synthesis of polydopamine microvesicles (PDA MVs). These PDA MVs exhibit an approximate diameter of 1 µm, showcasing a pliable structure reminiscent of cellular morphology. Through modifications of antibodies on the surface of PDA MVs, their capacity as artificial antigen presentation cells is evaluated. In comparison to solid nanoparticles, PDA MVs with cell-like structures show enhanced T-cell activation, resulting in a 1.5-fold increase in CD25 expression after 1 day and a threefold surge in PD-1 positivity after 7 days. In summary, the research elucidates the influence of nucleation and interfacial assembly in microemulsion polymerization systems, providing a direct synthesis method for MVs and substantiating their effectiveness as artificial antigen-presenting cells.
研究领域:
生物材料学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2020
·
IF 3.383
Fan Zhao,Luchen Sun,Nanfei Yang,Wei Zheng,Pingping Shen,Yahong Huang,Yan Lu
Extensive literature has demonstrated that acute myeloid leukaemia (AML) cells show enhanced mitochondrial biogenesis and increased reliance on oxidative phosphorylation (OXPHOS) compared with normal hematopoietic progenitors, and one hallmark of AML leukaemia blasts is myeloid differentiation blockade. However, relatively few reports have linked these processes. Recent studies have indicated that therapies that overcome differentiation arrest represent an effective treatment strategy. Here, we identified that the disruption of the mitochondrial mass and energy metabolism promotes leukaemia cellular myeloid differentiation. In this study, we showed that acute monocytic leukaemia (AML-M5) cells package mitochondria in microvesicles (MVs) when MVs shed from membranes. Additionally, during myeloid differentiation, we report for the first time that differentiated leukaemia cells release more MVs than undifferentiated leukaemia cells. Targeting the formation of MVs using a specific inhibitor (Y-27632) restrained myeloid differentiation, suggesting that the increased release level of MVs plays an important role in regulating myeloid differentiation. Furthermore, the intracellular mitochondria and ATP levels were decreased after leukaemia cells overcame the differentiation blockade. Moreover, rotenone , which is used to inhibit the respiratory chain and ATP production, had a strong effect on myeloid differentiation in monocytic leukaemia cells. Collectively, these studies uncovered the relationship between mitochondrial function and myeloid differentiation and may provide more insight into the diagnosis and treatment of AML.
研究领域:
血液学
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肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 30
·6378-6389
·
IF 5.344
Zhuo Liang,Yue Luo,Yonggang Lv
A demineralized bone matrix (DBM) scaffold has good biocompatibility, low antigenicity, a natural porous structure and no cytotoxicity, and so it is an appropriate material for bone regeneration. However, osteoinductive growth factors are often removed during preparation, which destroys the osteoinductive capacity of the DBM scaffold. Biomaterials combined with gene therapy is a promising approach to effectively avoid this adverse side effect. This study develops a human bone morphogenetic protein 2 (hBMP2) gene-activated DBM scaffold to enhance the osteoinductive capacity of DBM and improve bone repair. Bone marrow mesenchymal stem cell (MSC)-derived microvesicles (MVs) were obtained, and polyethyleneimine (PEI) and human bone morphogenetic protein 2 (hBMP2) plasmids (phBMP2) were sequentially coated on the MVs by layer-by-layer (LBL) self-assembly to form an MVs–PEI/phBMP2 non-viral gene vector. Finally, the gene-activated scaffold (DBM/MVs–PEI/phBMP2) was prepared by loading MVs–PEI/phBMP2 onto a DBM scaffold. The experimental results show that the MVs–PEI/phBMP2 exhibits higher transfection efficiency and lower cytotoxicity to MSCs when the MVs/PEI weight ratio = 5, and could enhance the osteogenic differentiation of MSCs in vitro. Subcutaneous implantation into rats showed that the DBM/MVs–PEI/phBMP2 scaffold could efficiently enhance the deposition of: collagen fibers, osteocalcin, osteopontin and CD34 endogenous proteins. Rabbit femoral condyle defect experiments proved that the DBM/MVs–PEI/phBMP2 scaffold could significantly promote bone repair. This study presents a novel, highly efficient and low cytotoxicity gene delivery vector based on MVs. The gene-activated DBM scaffold based on MVs not only could promote bone formation but also angiogenesis, implying that this kind of gene-activated scaffold is a promising bone substitute material.
研究领域:
组织工程
·
再生医学
·
基因治疗
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Ding Wu,Yi Yu,Dan Jin,Meng-Meng Xiao,Zhi-Yong Zhang,Guo-Jun Zhang
Cancerous microvesicles (MVs), which are heterogeneous membrane-bound nanovesicles shed from the surfaces of cancer cells into the extracellular environment, have been widely recognized as promising “biofingerprints” for various cancers. High-performance identification of cancerous MVs plays a vital role in the early diagnosis of cancer, yet it is still technically challenging. Herein, we report a gold nanoparticle (AuNP)-decorated, dual-aptamer modified reduced graphene oxide (RGO) field-effect transistor (AAP-GFET) nanosensor for the label-free, specific, and sensitive quantification of HepG2 cell-derived MVs (HepG2-MVs). After GFET chips were fabricated, AuNPs were then decorated on the RGO surface. For specific capture and detection of HepG2-MVs, both sulfhydrylated HepG2 cell specific TLS11a aptamer (AptTLS11a) and epithelial cell adhesion molecule aptamer (AptEpCAM) were immobilized on the AuNP surface through an Au–S bond. This developed nanosensor delivered a broad linear dynamic range from 6 × 105 to 6 × 109 particles/mL and achieved a high sensitivity of 84 particles/μL for HepG2-MVs detection. Moreover, this AAP-GFET platform was able to distinguish HepG2-MVs from other liver cancer-related serum proteins (such as AFP and CEA) and MVs derived from human normal cells and other cancer cells of lung, pancreas, and prostate, suggesting its excellent method specificity. Compared with those modified with a single type of aptamer alone (AptTLS11a or AptEpCAM), such an AAP-GFET nanosensor showed greatly enhanced signals, suggesting that the dual-aptamer-based bio–nano interface was uniquely designed and could realize more sensitive quantification of HepG2-MVs. Using this platform to detect HepG2-MVs in clinical blood samples, we found that there were significant differences between healthy controls and hepatocellular carcinoma (HCC) patients, indicating its great potential in early HCC diagnosis.
研究领域:
生物传感器
·
纳米技术
·
癌症诊断
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Zhenkang Liang,Zehong Chen,Chaowei Zhang,Cui Chen,Wende Yang,Yuxuan Zhang,Hongbo Wei
Purpose Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms.Methods We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment.Results The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it.Conclusion MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.
研究领域:
泌尿外科
·
细胞生物学
·
分子生物学
·
神经外科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Ming Jia,Wei Ren,Yan Liu,Chenglong Wang,Xiu Zheng,Dan Zhang,Xiaoqiu Tan,Chunhong Li
Dysregulation of superoxide anion (O2–) and hydrogen peroxide (H2O2) metabolism in the microenvironment of rheumatoid arthritis (RA) drives the feedback loops of TNF-α and IL-1β thereby inducing an inflammatory storm between immune cells and joint tissue cells. Here, we combine nanoscale manganese dioxide (MnO2) with microvesicles derived from macrophage (MMV). The former possesses superoxide dismutase (SOD) and catalase (CAT)-like activities that can modulate this imbalance, and we amplify the enzyme-like activities by using the amorphous hollow mesoporous structure and surface modification. The latter is a natural endogenous component with the parent cell-like inflammatory homing ability and a unique function of transmitting information to surrounding and distant cells (″messenger function″), which helps amorphous hollow MnO2 (H–MnO2) nanozymes to cloak in the blood and reach the site of inflammation, where they can not only accumulate in activated macrophages but also pretend to be ″messengers″ that are utilized by fibroblast-like synoviocytes (FLS) and chondrocytes. In addition, we also load dexamethasone sodium phosphate (DSP) for helping the nanozymes work. Messenger nanozyme (MMV-MnO2@DSP) inherits the natural properties of MMV and mimics the enzymatic activity of SOD and CAT. It accumulates in activated macrophages to restore the metabolism of O2– and H2O2 while promoting repolarization and inhibits the feedback loops of TNF-α and IL-1β among macrophages, fibroblast-like synoviocytes, and chondrocytes, leading to anti-rheumatoid arthritis effects in vitro and in vivo.
研究领域:
免疫学
·
纳米技术
·
药理学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Zhechang Chen,Caijie Yuan,Yaxin Ye,Bitao Lu,Enling Hu,Fei Lu,Kun Yu,Ruiqi Xie,Guangqian Lan
Arterial thrombosis is a critical thrombotic disease that poses a significant threat to human health. However, the existing clinical treatment of arterial thrombosis lacks effective targeting and precise drug release capability. In this study, we developed a system for targeted delivery and on-demand release in arterial thrombosis treatment. The carrier was constructed using chitosan (CS) and fucoidan (Fu) through layer-by-layer assembly, with subsequent surface modification using cRGD peptide. Upon encapsulation of urokinase-type plasminogen activator (uPA), the resulting therapeutic drug delivery system, uPA-CS/Fu@cRGD, demonstrated dual-targeting abilities towards P-selectin and αIIbβ3, as well as pH and platelet-responsive release properties. Importantly, we have demonstrated that the dual targeting effect exhibits higher targeting efficiency at shear rates simulating thrombosed arterial conditions (1800 s −1 ) compared to single targeting for the first time. In the mouse common iliac artery model, uPA-CS/Fu@cRGD exhibited great thrombolytic capability while promoting the down-regulation of coagulation factors (FXa and PAI-1) and inflammatory factors (TNF-α and IL-6), thus improving the thrombus microenvironment and exerting potential in preventing re-occlusion. Our dual-target and dual-responsive, fucoidan-based macrovesicle represent a promising platform for advanced drug target delivery applications, with potential to prevent coagulation tendencies as well as improving thrombolytic and reducing the risk of re-occlusion.
研究领域:
药学
·
生物医学工程
·
血栓研究
·
药物递送系统
✓ 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）