Bioactive Materials
·
2025
·
IF 20.3
Tianliang Ma,Qimeng Liu,Zheyu Zhang,Jiangyu Nan,Guanzhi Liu,Yute Yang,Yihe Hu,Jie Xie
The onset of periprosthetic osteolysis is mediated by wear particles following artificial arthroplasty. This manifests as a disturbed bone metabolism microenvironment, characterized by insufficient osteogenesis and angiogenesis, and enhanced osteoclastic activity. To target and remodel the homeostatic environment of bone metabolism in the sterile region around the prosthesis, we successfully pioneered the proposal and construction of a fused exosome (f-exo) system with M2 macrophage-derived exosomes (M2-exo) and urine-derived stem cell exosomes (USC-exo). The results demonstrate that f-exo effectively combines the osteolysis region-targeting capabilities of M2-exo with the bone metabolic homeostasis modulation effects of two exosomes (M2-exo and USC-exo), thereby achieving a significantly enhanced bone metabolic homeostasis targeting effect in the periprosthetic osteolysis region. The proteomic analysis of M2-exo, USC-exo, and f-exo revealed the potential mechanism of f-exo in targeting-regulation of bone metabolic homeostasis. Our study employs an innovative approach utilizing the fused exosome system for exosome targeted delivery, which offers a novel intervention strategy for the clinical management of periprosthetic osteolysis. Furthermore, it provides a novel conceptual framework for the development of exosome-based drug-targeting delivery systems.
研究领域:
骨科
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再生医学
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组织工程
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外泌体治疗
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产品关联
DOI
PubMed
高影响因子
Diagnostics
·
2022
·Vol. 12
·期 2
·239
·
IF 3.992
Yingying Xie,Wenwen Chen,Mengqian Zhao,Yuhai Xu,Hao Yu,Jianhua Qin,Hongjing Li
Arthritis is caused by inflammation, infection, degeneration, trauma, or other factors that affect approximately 250 million people all over the world. Early diagnosis and prediction are essential for treatment. Exosomes are nanoscale vesicles that participate in the process of joint disease. Serum is the mainly used sources in the study of arthritis-related exosomes, while whether serum exosomes can reflect the contents of synovial fluid exosomes is still unknown. In this work, we separated exosomes from serum and the synovial fluid of osteoarthritis patients and compared their miRNA expression utilizing miRNA sequencing. The results revealed that 31 upregulated and 33 downregulated miRNAs were found in synovial fluid compared to serum. Transcriptome analysis showed that these differentially expressed miRNAs were mainly associated with intercellular processes and metabolic pathways. Our results show that serum-derived exosomes cannot fully represent the exosomes of synovial fluid, which may be helpful for the study of joint diseases and the discovery of early diagnostic biomarkers of arthritis.Keywords:exosomes;miRNA;synovial fluid;arthritis
研究领域:
生物标志物发现
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分子生物学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2024
·
IF 3.8
Ying Zhang,Jing Xie,Huimin Zhang,Jiacheng Li,Xing Mi,Xuyi Zhou,Zhenhua Ding
Introduction Local exposure to ionizing radiation (IR) can induce changes in biological processes in distant tissues and organs. Exosomes are nanoscale vesicles that transport biomolecules, mediate communication between cells and tissues, and can affect the abscopal effects of radiotherapy. Methods Mice were treated with 8.0 Gy doses of chest and abdomen IR, after which serum samples were taken 24 h after exposure. Their serum exosomes were then isolated via ultracentrifugation and the small RNA portions were extracted for sequencing and bioinformatic analysis. Exosomes were injected intravenously into the mice to assess their ability to cross the blood-brain barrier (BBB). Glioma cells and gliomal stem cells (GSCs) were examined for malignant biological behaviors, stemness, and tumorigenic capacity after co-culturing with different types of exosomes. Results We found that serum exosomes crossed the BBB in mice after local IR exposure—which induced decreases in the expression of BBB tight-junction proteins and increased brain endothelial cell apoptosis. Exosomes from the exposed groups promoted malignant biological behaviors, stemness, and tumorigenic capacity in glioma cells and GSCs by upregulating the expression of SOS1. Phospho-MEK1/2 and Phospho-ERK1/2, of the MAPK signaling pathway, were found to be up-regulated in cells that were co-cultured with the exposing groups of the exosomes. Further analyses demonstrated that differentially expressed levels of miR-93-5p in mouse serum exosomes regulated the cellular expression of SOS1. Conclusion Following local IR exposure, serum exosomes cross the BBB to promote the progression of distant gliomas. Exosomal microRNAs play an important role in this process.
研究领域:
肿瘤学
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分子生物学
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放射生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2020
·
IF 5.977
Juqian Jiang,Yongqi Yu,Hui Zhang,Chenxin Cai
Exosomes are extracellular nanovesicles for transferring and delivering membrane and cytosolic molecules between cells. Detection and profiling of exosomal proteins can provide direct information on disease progression, which is important to the early diagnosis and monitoring of diseases. Herein, a well-designed electrochemical aptasensor was fabricated for the profiling of cancerous exosomal proteins based on DNA nanotetrahedron (NTH) coupled with Au nanoparticles (NPs) and enzymatic signal amplification. In this assay, the aptamer modified DNA NTHs were used as the recognition and capture unit, Au NPs-DNA conjugates coupled with horseradish peroxidase were used to realize signal amplification. This aptasensor achieves a detection limit down to 1.66 × 10 4 particles/mL for HepG2 liver cancer exosomes. In addition, the analysis of plasma-derived exosomes in HepG2 liver cancer bearing mice at different cancer stages was also achieved. More importantly, the aptasensor can be used to profile four kinds of exosomal proteins by using the corresponding aptamer. The proposed electrochemical aptasensor may be served as a potential platform for exosome detection and exosomal proteins profiling.
研究领域:
生物化学
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纳米技术
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癌症研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
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IF 10.257
Yanyan Yu,Wei S. Zhang,Yuehua Guo,Huaping Peng,Min Zhu,Dandan Miao,Gaoxing Su
Tumor-derived exosomes containing multiple proteins originating from parent cancer cells have emerged as biomarkers for cancer diagnosis. Herein, we propose a three-dimensional DNA motor-based exosome assay platform for the selective and sensitive detection of exosomes. The DNA motor used gold nanoparticle (GNP) tracks, consisting of fluorescein-labeled substrate strands and aptamer-locked motor strands. Recognition of the target protein on exosomes by its aptamer unlocked the motor strand and triggered the DNA motor process. Powered by restriction endonuclease , the motor strands autonomously walked along the GNP track. Each movement step cleaved one substrate strand and restored one fluorescein molecule. For exosome detection, the proposed method displayed a broad dynamic range acrossing 5 orders of magnitude with the detection limit as low as 8.2 particles/μL in PBS. The method also exhibited good selectivity among different tumor-derived exosomes and performed well in complex biological samples. The capability to profile exosomal surface proteins efficiently endowed our DNA motor great potential for developing a simple and cost-effective device for clinical diagnosis.
研究领域:
生物医学工程
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分子生物学
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癌症诊断
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Micromachines
·
2021
·Vol. 12
·期 10
·1182
·
IF 2.891
Wenwen Chen,Yingying Xie,Yuang Chang,Yuhai Xu,Mengqian Zhao,Pengwei Deng,Jianhua Qin,Hongjing Li
Exosomes are membrane-bound nanovesicles secreted by most types of cells, which contain a series of biologically important molecules, such as miRNAs, proteins, and lipids, etc. Emerging evidence show that exosomes can affect the physiological status of cells and are involved in various pathological processes. However, due to their small size and density close to body fluids, it is challenging to separate exosomes from a small volume of biological samples in a simple manner. Herein, we propose a new strategy for isolating circulating exosomes from biological samples in a portable device. This method synergistically integrates chitosan electrostatic-adsorption, scaffold substrates, and shuttle flow to enable the highly effective capture of circulating exosomes with a recovery rate of over 80% within 20 min, which is much better than the performance of traditional ultracentrifugation (5–25%, 3 h). Besides, the isolated exosomes from samples could be lysed in situ and further subjected to RNA concentration detection and protein analysis. In particular, all the necessary procedures for exosome separation could be integrated into a single device without the need for bulky equipment. This established device is portable and easy to operate, which provides a promising platform for the study of exosome biology and clinical diagnosis.Keywords:exosome;separation;chitosan scaffold
研究领域:
生物技术
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纳米技术
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医学诊断
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分子生物学
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产品关联
DOI
PubMed
高影响因子
VIEW
·
2024
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IF 9.7
Jie Luo,Binpan Wang,Xiaoqi Tang,Ping Huang,Sha Yang,Shuang Zhao,Shuang Xie,Qiaofeng Li,Kai Chang,Ming Chen
Tumor-derived exosomes are crucial for early non-invasive and accurate tumor diagnosis in clinical diagnostics. The development of highly sensitive, simple, and intuitive exosome assays has sparked a research upsurge in clinical diagnostics. Here, we develop a bio-responsive intelligent DNA hydrogel loaded with CRISPR/Cas12a for universal and ultrasensitive detection of the exosomes. The aptamer serves as the target response unit and switch, competitively disintegrating the region of the DNA linkers and then Cas12a/crRNA was released and activated, resulting in a high fluorescent intensity for exosome detection at the detection limit of 119 particles/μL. Moreover, a constructed colorimetric tube is made by loading a colorimetric filter membrane on the tube lid and intelligent DNA hydrogel on the tube bottom, which enables one-pot portable colorimetric detection. Without the need for laboratory instruments and professionals, this strategy allows for naked eye detection with limit of detection as low as 10 4 particles/μL, and shows great applicability in distinguishing between healthy individuals, pretreatment patients, and post-treatment patients after obtaining a testable analyte. In this study, an ultrasensitive detection platform for exosomes that enables one-step sensing and dual signal output was introduced. The findings here suggest that this platform is a promising tool for the application of liquid biopsy based on exosomes in clinical diagnosis.
研究领域:
生物技术
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分子生物学
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临床诊断
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纳米技术
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癌症研究
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产品关联
DOI
高影响因子
BMC Urology
·
2023
·Vol. 23
·期 1
·1-11
·
IF 2
Pan Gaojian,Jiang Bo,Yi Zhongquan,Yin Jiuhu,Liu Yadong
Bladder cancer stem cells (BCSCs) are considered as the root cause of BC initiation and recurrence, and exosomes derived from BCSCs (CSCs-exo) are the vital tool for establishing a stable tumor microenvironment. miR-105-5p has been revealed to promote tumor growth in a variety of cancers, but the effects on BC are still not included.Characteristics of CSCs-exo were examined by transmission electron microscope and nanoparticle tracking analysis. PKH67 dye was used to observe the cellular uptake of exosomes. Cell viability, migration and invasion were detected by CCK-8, wound healing and transwell invasion assays, respectively. The interaction between miR-105-5p and GPR12 was verified by luciferase activity assay. Xenografts were induced in the nude mice, and H&E staining method was applied to analyze the histological changes of xenografts. CSCs-exo efficiently promoted BC cell viability, migration and invasion. miR-105-5p was highly expressed in CSCs and CSCs-exo treatment significantly upregulated the expression of miR-105-5p in BC cells.GPR12 was subsequently verified to be the target gene of miR-105-5p, and overexpression of GPR12 abrogated the effects of miR-105-5p on BC cell growth and metastasis. Reversely, the anti-tumor function of miR-105-5p antagomir was observed in the xenograft mice.CSCs aggravated the malignancy of BC partly through transmitting exosomal miR-105-5p to BC cells to inhibit the expression of GPR12, which developed a novel aspect for CSC-targeted therapies.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Small Methods
·
2022
·Vol. 6
·期 6
·2200236
·
IF 15.367
Hanxu Chen,Feika Bian,Jiahui Guo,Yuanjin Zhao
Tumor-derived exosomes are vital for clinical dynamic and accurate tumor diagnosis, thus developing sensitive and multiple exosomes detection technology has attracted remarkable attention of scientists. Here, a novel herringbone microfluidic device with aptamer-functionalized barcodes integration for specific capture and multiple detection of tumor-derived exosomes is presented. The barcodes with core–shell constructions are obtained by partially replicating the periodically ordered hexagonal close-packaged colloidal crystal beads. As their inverse opal hydrogel shell possesses rich interconnected pores, the barcodes could provide abundant surface area for functionalization of DNA aptamers to realize specific recognition of target exosomes. Besides, the encoded structure colors of the barcodes can be maintained stably during the detection events as their hardish cores are with sufficient mechanical strength. It is demonstrated that by embedding these barcodes in herringbone groove microfluidic device with designed patterns, the specific capture efficiency and synergetic detection of multiple tumor-derived exosomes in peripheral blood can be significantly improved due to enhanced resistance of turbulent flow. These features make the aptamer-functionalized barcodes and herringbone microfluidics integrated platform promising for exosomes extraction and dynamic tumor diagnosis.
研究领域:
生物医学工程
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微流控技术
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癌症诊断
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Wang Da,Bai Yunfei,Cheng Guogang,Shen Shengqiang,Xiao Gengwu,Ma Demei,Zhao Ganggang,Chen Wei,Li Tianshi,Zhang Litao,Ge Xiaohu
Artesunate (ATS) is considered the most widely employed artemisnin derivative in the treatment of Plasmodium falciparum malaria. However, poor solubility and low bioavailability of ATS limit its further clinical application. Herein, we developed a new strategy based on the exosome (exo) - drug conjugation (EDC) using the milk-derived exosomes for ATS delivery. The Exo-ATS conjugates (EACs) which formed via a facile bio-conjugation of ATS to the exosomal surface, have been demonstrated to be able to not only boost the solubility and bioavailability of ATS but also enable a sustained-release of ATS from exosomes. Maximal improvement of 71.4-fold in the solubility of ATS was attained by EACs. The corresponding entrapment efficiency and drug loading capacities were found to be 90.3% and 73.9% for EACs, respectively. Further, in vivo pharmacokinetics study manifested that maximum 2.6-fold improved bioavailability of ATS was achieved by oral delivery of EACs. Moreover, EACs displayed a distinct sustained-release profile of maximum 36.2-fold prolonged half-life of ATS via intravenous delivery. We reported that for the first time the administration of EACs could be a potential drug delivery strategy aimed at ameliorating the pharmacokinetic profile of ATS based on our encouraging results and hoped that our work opened up a new avenue for the development of EDC delivery system.
研究领域:
药学
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药物递送系统
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药理学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
·
IF 4.8
Yiren Xiong,Guoqiang Guo,Hongyi Xian,Zuqing Hu,Di Ouyang,Jiayi He,Shanshan He,Renyi Liu,Zhenjie Gao,Meilin Tang,Ying Chen,Suqin Tan,Xiaoqi Zhu,Abudumijiti Abulimiti,Sujin Zheng,Hehai Huang,Dalin Hu
Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.
研究领域:
毒理学
·
细胞生物学
·
环境科学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF DERMATOLOGICAL RESEARCH
·
2025
·Vol. 317
·期 1
·1-16
·
IF 2.1
Lin Ling,Li Wei,Gao Xinjing,Li Qian,Zhou Xin,Liu Weiyu,Zhong Xuelian,Yang Yunqing,Zhang Xibao,Luo Quan
Psoriasis represents a chronic inflammatory skin disease occurring globally. We investigated the role of plasma exosomal microRNA (miR)- 148a- 3p and its target gene Bim in psoriasis. Plasma exosomes (Exos) and CD4 + T cells were extracted from psoriatic patients. miR- 148a- 3p expression in Exos and CD4 + T cells of psoriatic patients, the proportions of CD4 + T cell subsets, and the contents of anti-inflammatory/pro-inflammatory factors were determined by RT-qPCR, flow cytometry and ELISA. The correlation between plasma exosomal miR- 148a- 3p and CD4 + T cell subsets in psoriatic patients was analyzed by Pearson’s analysis. The psoriatic mouse was treated with Exos/antagomir miR- 148a- 3p. Histopathological changes in the skin were observed. The CD4 + T cell subset levels, serum cytokine contents and miR- 148a- 3p expression in the blood were measured. The miR- 148a- 3p-Bim targeted binding relationship was predicted and verified by Starbase database and dual-luciferase assay. The Bim expression in psoriatic mice was determined. Psoriatic patients had highly-expressed miR- 148a- 3p in both Exos and CD4 + T cells, and abnormal CD4 + T cell subsets and cytokine levels. Plasma exosomal miR- 148a- 3p was correlated with the CD4 + T cell subsets in psoriatic patients. Exos caused down-regulated miR- 148a- 3p level in skin tissues of mouse, regulated CD4 + T cell function and aggravated the symptoms in psoriatic mice. miR- 148a- 3p repression partially reversed the role of Exos in CD4 + T cell function and psoriasis-like symptoms. Exos-carried miR- 148a- 3p targeted Bim in CD4 + T cells of psoriatic mice. Plasma exosomal miR- 148a- 3p targeted Bim to affect the dysfunction of CD4 + T cells in psoriatic mice, thereby aggravating the psoriasis-like symptoms.
研究领域:
皮肤病学
·
分子生物学
·
免疫学
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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）