ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Li Li,Zhiyu Wang,Kepeng Wang,Siyuan Fu,Dan Li,Mao Wang,Yi Cao,Houjuan Zhu,Ziyan Li,Lixing Weng,Zhiyang Li,Xianguang Ding,Lianhui Wang
The treatment of cutaneous wounds involving complex biological processes has become a significant public health concern worldwide. Here, we developed an efficient extracellular vesicle (EV) ink to regulate the inflammatory microenvironment and promote vascular regeneration for wound healing. The technology, termed portable bioactive ink for tissue healing (PAINT), leverages bioactive M2 macrophage-derived EVs (EVM2) and a sodium alginate precursor, forming a biocompatible EV-Gel within 3 min after mixing, enabling it to be smeared on wounds in situ to meet diverse morphologies. The bioactive EVM2 reprogram macrophage polarization and promote the proliferation and migration of endothelial cells, thereby effectively regulating inflammation and enhancing angiogenesis in wounds. Through integration with a 3D printing pen, the platform enables EV-Gel to be applied to wound sites having arbitrary shapes and sizes with geometric matches for tissue repairment. When evaluated using a mouse wound model, PAINT technology accelerates cutaneous wound healing by promoting the angiogenesis of endothelial cells and the polarization of macrophages to M2 phenotype in vivo, demonstrating the high potential of bioactive EV ink as a portable biomedical platform for healthcare.
研究领域:
生物医学工程
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组织工程
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2023
·
IF 12.4
Dehong Tan,Wenxiang Zhu,Lujie Liu,Yuanwei Pan,Yangtao Xu,Qinqin Huang,Lingling Li,Lang Rao
Background: Safe and effective wound healing can be a major clinical challenge. Inflammation and vascular impairment are two main causes of inadequate wound healing. Methods: Here, we developed a versatile hydrogel wound dressing, comprising a straightforward physical mixture of royal jelly-derived extracellular vesicles (RJ-EVs) and methacrylic anhydride modified sericin (SerMA), to accelerate wound healing by inhibiting inflammation and promoting vascular reparation. Results: The RJ-EVs showed satisfactory anti-inflammatory and antioxidant effects, and significantly promoted L929 cell proliferation and migration in vitro . Meanwhile, the photocrosslinked SerMA hydrogel with its porous interior structure and high fluidity made it a good candidate for wound dressing. The RJ-EVs can be gradually released from the SerMA hydrogel at the wound site, ensuring the restorative effect of RJ-EVs. In a full-thickness skin defect model, the SerMA/RJ-EVs hydrogel dressing accelerated wound healing with a healing rate of 96.8% by improving cell proliferation and angiogenesis. The RNA sequencing results further revealed that the SerMA/RJ-EVs hydrogel dressing was involved in inflammatory damage repair-related pathways including recombinational repair, epidermis development, and Wnt signaling. Conclusion: This SerMA/RJ-EVs hydrogel dressing offers a simple, safe and robust strategy for modulating inflammation and vascular impairment for accelerated wound healing.
研究领域:
生物医学工程
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组织工程
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Qiang Li,Saisong Zhan,Xiaoqing Yang,Zhaowei Zhang,Ning Sun,Xiang Wang,Jingjing Kang,Rui Du,Xiaoqin Hong,Minghao Yue,Xiaomin Li,Yujing Tang,Guangming Liu,Yue Liu,Dingbin Liu
Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases (n = 48), cystitis patients (n = 27), and healthy donors (n = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases (n = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.
研究领域:
癌症生物学
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纳米技术
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生物标志物发现
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医学诊断
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2018
·Vol. 9
·期 1
·1-15
·
IF 12.353
Usman Waqas Muhammad,Pham Tin Chanh,Kwok Yuk Yan,Vu Luyen Tien,Ma Victor,Peng Boya,Chan Yuen San,Wei Likun,Chin Siew Mei,Azad Ajijur,He Alex Bai-Liang,Leung Anskar Y. H.,Yang Mengsu,Shyh-Chang Ng,Cho William C.,Shi Jiahai,Le Minh T. N.
Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR–Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.
研究领域:
药理学
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分子生物学
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基因治疗
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生物技术
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产品关联
DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2024
·Vol. 13
·期 6
·e12467
·
IF 15.5
Danyu Li,Siyi Zou,Ziyang Huang,Congcong Sun,Guozhen Liu
Extracellular vesicles (EVs) carry disease-specific molecular profiles, demonstrating massive potential in biomarker discovery. In this study, we developed an integrated biochip platform, termed EVID-biochip (EVs identification and detection biochip), which integrates in situ electrochemical protein detection with on-chip antifouling-immunomagnetic beads modified with CD81 antibodies and zwitterion molecules, enabling efficient isolation and detection of neuronal EVs. The capability of the EVID-biochip to isolate common EVs and detect neuronal EVs associated with Parkinson's disease in human serum is successfully demonstrated, using the transmembrane protein L1-cell adhesion molecule (L1CAM) as a target biomarker. The EVID-biochip exhibited high efficiency and specificity for the detection of L1CAM with a sensitivity of 1 pg/mL. Based on the validation of 76 human serum samples, for the first time, this study discovered that the level of L1CAM/neuronal EV particles in serum could serve as a reliable indicator to distinguish Parkinson's disease from control groups with AUC = 0.973. EVID-biochip represents a reliable and rapid liquid biopsy platform for the analysis of complex biofluids offering EVs isolation and detection in a single chip, requiring a small sample volume (300 µL) and an assay time of 1.5 h. This approach has the potential to advance the diagnosis and biomarker discovery of various neurological disorders and other diseases.
研究领域:
神经学
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生物医学工程
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生物标志物发现
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诊断学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-33
·
IF 10.6
Liu Jianyu,Wang Meiqun,Tian Xiaoyan,Wu Shuhong,Peng Haisen,Zhu Yaqiong,Liu Yuehui
Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR. Graphical Abstract
研究领域:
免疫学
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分子生物学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Ying Jiang,Lei Wang,Pengjuan Zhang,Xuehui Liu,Huixia Di,Jie Yang,Shu-Lin Liu,Dai-Wen Pang,Dingbin Liu
Extracellular vesicles (EVs) are intercellular communicators that are heavily implicated in diverse pathological processes. However, it is poorly understood how EVs interact with recipient cells due to the lack of appropriate tracking techniques. Here, we report a robust chemoenzymatic labeling technique for visualizing the internalization process of EVs into target cells in real time. This method uses phospholipase D (PLD) to catalyze the in situ exchange of choline by alkyne in the native EV phosphatidylcholine. Subsequent alkyne–azide click chemistry allows conjugation of Cy5 dyes for visualizing EVs internalization by confocal fluorescence microscopy. The fluorescent labeling of EVs was accomplished in an efficient and biocompatible way, without affecting both the morphology and biological activity of EVs. We applied this chemoenzymatic labeling strategy to monitor the cellular uptake of cancer cell-derived EVs in real time and to further reveal multiple internalization mechanisms. This robust, biocompatible labeling strategy provides an essential tool for EV-related studies ranging from chemical biology to drug delivery.
研究领域:
细胞生物学
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分子生物学
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生物技术
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-13
·
IF 10.2
Zhang Yue,Pan Deng,Ning Zhenqiang,Huang Fang,Wei Yiting,Zhang Mingming,Zhang Yuanjian,Wang Li-xin,Shen Yanfei
Tumor cell-released LC3 + extracellular vesicles (LC3 + EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3 + EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3 + EVs levels with high sensitivity to identify LC3 + EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3 + EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3 + EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3 + EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics.
研究领域:
癌症生物学
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生物医学工程
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电化学
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生物标志物研究
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临床诊断
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Chunhui Ma,Tao Wang,Xinmeng Jin,Wanglin Zhang,Qi Lv
Repairing cartilage/subchondral bone defects that involve subchondral bone is a major challenge in clinical practice. Overall, the integrated repair of the structure and function of the osteochondral (OC) unit is very important. Some studies have demonstrated that the differentiation of cartilage is significantly enhanced by reducing the intake of nutrients such as lipids. This study demonstrates that using starvation can effectively optimize the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs). A hyaluronic acid (HA)-based hydrogel containing starved BMSCs-EVs displayed continuous release for more than 3 weeks and significantly promoted the proliferation and biosynthesis of chondrocytes around the defect regulated by the forkhead-box class O (FOXO) pathway. When combined with vascular inhibitors, the hydrogel inhibited cartilage hypertrophy and facilitated the regeneration of hyaline cartilage. A porous methacrylate gelatine (GelMA)-based hydrogel containing calcium salt loaded with thrombin rapidly promoted haematoma formation upon contact with the bone marrow cavity to quickly block the pores and prevent the blood vessels in the bone marrow cavity from invading the cartilage layer. Furthermore, the haematoma could be used as nutrients to accelerate bone survival. The in vivo experiments demonstrated that the multifunctional lineage-specific hydrogel promoted the integrated regeneration of cartilage/subchondral bone. Thus, this hydrogel may represent a new strategy for osteochondral regeneration and repair.
研究领域:
组织工程
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再生医学
·
骨科
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干细胞生物学
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生物材料
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Yutong Chen,Mengru Zhu,Shihao Sheng,Huijian Yang,Qin Zhang,Xiao Chen,Ke Xu,Mengmeng Li,Biaotong Huang,Qinglin Han,Yingying Jiang,Jiacan Su
Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mineral density and a heightened risk of fractures. Therapies for OP have primarily focused on balancing bone formation and bone resorption, but enhancing the remineralization of osteoporotic bone is also a key strategy for effective repair. Recent insights into biomineralization mechanisms have highlighted the essential role of mineral-containing extracellular vesicles (EVs) secreted by osteoblasts in promoting bone marrow mesenchymal stromal/stem cell (BMSC) differentiation and initiating matrix mineralization. Drawing from these principles, we developed a biomimetic approach to replicate the structure and function of the osteoblast-derived EVs by engineering biomimetic mitochondrial minerals with bone marrow homing cell membranes (CMs). This bone-targeted biomimetic system exhibits excellent biocompatibility, enhancing osteogenic differentiation and stimulating angiogenesis by regulating cellular energy metabolism. Additionally, the CM-coated structure shows affinity for collagen fibrils, effectively enhancing intrafibrillar collagen mineralization, thereby facilitating osteoporotic bone repair. Overall, the biomimetic system offers a safe and efficient therapeutic alternative, positioning it as a platform for bone tissue engineering and regenerative medicine.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
骨科
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细胞生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Chaoxiang Chen,Xueping Pan,Mengdi Sun,Jialin Wang,Xueqi Su,Tianyu Zhang,Yulei Chen,Daren Wu,Jian Li,Shuqi Wu,Xiaomei Yan
Extracellular vesicles (EVs) are recognized as potential candidates for next-generation drug delivery systems. However, the inherent cancer-targeting efficiency is unsatisfactory, necessitating surface modification to attach cell-binding ligands. By utilizing phospholipase D from Streptomyces in combination with maleimide-containing primary alcohol, the authors successfully anchored ligands onto milk-derived EVs (mEVs), overcoming the issues of ligand leakage or functional alteration seen in traditional methods. Quantitative nano-flow cytometry demonstrated that over 90% of mEVs are effectively modified with hundreds to thousands of ligands. The resulting mEV formulations exhibited remarkable long-term stability in conjugation proportion, ligand number, size distribution, and particle concentration, even after months of storage. It is further shown that conjugating transferrin onto mEVs significantly enhanced cellular uptake and induced pronounced cytotoxic effects when loaded with paclitaxel. Overall, this study presents a highly efficient, stable, cost-effective, and scalable ligand conjugation approach, offering a promising strategy for targeted drug delivery of EVs.
研究领域:
药学
·
生物技术
·
癌症研究
·
药物递送
✓ 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）