Membranes
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2025
·Vol. 15
·期 5
·141
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IF 3.6
Ning Li,Hongbo Xin,Keyu Deng
Outer membrane vesicles (OMVs) are extracellular vesicles secreted by Gram-negative bacteria with diameters of 20–250 nm. OMVs contain various biologically active substances from their parent bacteria, such as proteins, lipids, and nucleic acids.Escherichia coliNissle 1917 (EcN) is a Gram-negative probiotic that resides in the human intestine. EcN-derived OMVs are pivotal in modulating intestinal immune responses. However, few studies have addressed the heterogeneity of EcN-derived OMVs in terms of size, significantly limiting the research on their clinical applications. Currently, there are a lack of feasible methods for obtaining EcN-derived OMVs of different sizes. To address this knowledge gap, we developed a membrane filtration method to isolate EcN-derived OMVs of varying sizes. In this study, we first used gradient filtration to isolate high-purity EcN-derived OMVs and conducted a proteomic analysis. Subsequently, we used membrane filtration to separate the EcN-derived OMVs by size. We successfully obtained EcN-derived OMVs of three specific sizes: <50 nm, 50–100 nm, and 100–300 nm. We then performed proteomic analyses of these EcN-derived OMVs and compared their protein profiles. Finally, we compared the ability of each EcN-derived OMV type to induce RAW264.7 macrophages to secrete the pro-inflammatory factor interleukin (IL)-1β and the anti-inflammatory factor IL-10. The EcN-derived OMVs contained 646 different proteins overall; those of different sizes contained different protein types. Among them, the EcN-derived OMVs in the <50 nm group contained significantly fewer proteins (262 different types in total) than those in the 50–100 nm (1603 types) and 100–300 nm (1568 types) groups. Furthermore, the <50 nm group had fewer membrane proteins (40) than the 50–100 nm (215) and 100–300 nm (209) groups. We also found that RAW264.7 macrophages secreted different concentrations of IL-1β and IL-10 following co-incubation with the three EcN-derived OMV types. The 50–100 nm EcN-derived OMV group showed a stronger effect in terms of inducing inflammatory cytokine secretion compared to the other two groups. This study provides direct experimental evidence that EcN-derived OMVs of different sizes exhibit heterogeneous properties.
研究领域:
微生物学
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免疫学
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蛋白质组学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
·
IF 19
Lujiao Wang,Song Yang,Tao Zhou,Siyu Yang,Pengyu Bi,Jiangyi Zhou,Qi Wang,Hai Qiao
Extracellular vesicles, such as Escherichia coli outer membrane vesicles (OMVs), have been widely explored as carriers for contrast agents, yet their application in ultrasound imaging remains limited. In this study, heat-responsive nB-OMVs are developed by loading n-butanol into OMVs (nB-OMVs). Upon heating, the decreased solubility of n-butanol triggered phase separation within the vesicles, resulting in enhanced ultrasound signals, including fundamental, harmonic, and subharmonic components. Experimental results demonstrated that nB-OMVs retained the native morphology of OMVs, along with their tumor-targeting accumulation and tumor growth inhibition capabilities. nB-OMVs injection induces red blood cell extravasation into tumors, under near-infrared (NIR) irradiation, these extravasated RBCs acted as photothermal mediators, generating a localized thermal environment that activated intratumoral nB-OMVs and further amplified the ultrasound signal. In B-mode and contrast-enhanced ultrasound (CEUS) imaging, tumor grayscale intensities increased by 4.6- and 8.5-fold, respectively. This work provides a promising strategy for ultrasound-based tumor imaging using extracellular vesicles.
研究领域:
医学影像学
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生物材料学
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肿瘤学
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DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
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IF 19
Donglin Cai,Zhelun Li,Wendong Gao,Yuqing Mu,Jiaying Liu,Yufeng Zhang,Xiaohan Mei,Jingjing Quan,Lan Xiao,Yin Xiao
The temporary transition of macrophages from a pro-inflammatory macrophages (M1) to an anti-inflammatory macrophages (M2) is crucial for tissue repair and regeneration processes. Selectively targeting M1 macrophages is preferred to modulate inflammatory responses. However, macrophage populations are inherently heterogeneous, and the competitive phagocytosis of nanoparticles (NPs) by these two subtypes has not been thoroughly investigated. This study establishes a 3D cell co-culture system to evaluate the competitive phagocytosis of M1-targeting NPs under dynamic fluidic flow conditions. Bacterial outer membrane vesicles (OMVs) are utilized as a “trojan horse” to decorate gold nanocage (AuNC), creating hybrid NPs (AuNC-OM) capable of selectively targeting M1 macrophages. It is noted that the selective uptake of AuNC-OM by M1 macrophages is mediated through phagocytosis-related receptors CD64 and CD14, which are highly expressed on the M1 macrophage surfaces. Furthermore, the study demonstrates that AuNC-OM selectively targets M1 macrophages without affecting the phagocytosis of M2 macrophages. Once internalized, the nanoparticles release anti-inflammatory drugs, effectively reversing the inflammation. The release of dexmedetomidine from AuNC-OM protects against lipopolysaccharide (LPS)-induced bone resorption in a mouse model. This study presents a novel system for accurately assessing the M1 macrophage-targeting capabilities and introduces an innovative strategy for M1 macrophage-targeted therapy.
研究领域:
免疫学
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纳米医学
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药理学
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DOI
高影响因子
ACS Applied Materials & Interfaces
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2025
·
IF 8.2
Han Yin,Jingqi Zhao,Hanyu Zhong,Nanxi Zhu,Yiyi Zhang,Jiyao Li,Jun Luo,Kunneng Liang,Bo Han,Jiaojiao Yang
Current treatments for skin infections employing single-agent antimicrobials have demonstrated pronounced limitations. Here, we have engineered an efficient antibacterial composite consisting of MXene and poly(vinyl alcohol) electrospun fibrous membranes, which are further functionalized with outer membrane vesicles (OMVs) using a tannic acid (TA) bridge. Upon near-infrared irradiation, OMVs augment the photothermal properties of MXene due to their “bedquilt effect”. Meanwhile, the temperature rise facilitates active antibacterial substance release by increasing the permeability of the OMVs. The synergistically enhanced antimicrobial ability of the OMVs and photothermal materials achieves a potentiated antibacterial effect, resulting in a near 100% antibacterial efficacy in vitro and in vivo. This multifunctional, antibiotic-free dressing membrane, which integrates photothermal and biological antibacterial properties, presents a promising therapeutic strategy for the management of skin wound infections.
研究领域:
材料科学
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医学
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生物工程
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DOI
PubMed
高影响因子
JOURNAL OF MICROENCAPSULATION
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2020
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IF 2.287
Jinyan Shi,Zhiwei Ma,Hao Pan,Yang Liu,Yuqi Chu,Jinglei Wang,Lijiang Chen
Aim In this study, 5-fluorouracil (5-FU) is delivered to target colon without the interference of mononuclear phagocyte system (MPS).Methods Outer membrane vesicles (OMVs) were used as the biological shield to disguise mesoporous silica (MSN) and 5-FU. OMVs-MSN-5-FU were prepared by high pressure co-extrusion, and characterised on the basis of size, drug loading, transmission electron microscope, infra-red spectroscopy, differential scanning calorimetry, thermal gravity analysis, % in vitro release, MTT assay, cell uptake and in vivo imaging.Results OMVs-MSN-5-FU with −18.22 ± 0.17 mV zeta potential and 90.4 ± 9.1 nm size were used for oral treatment of colon cancer. Drug loading of the drug was 50.22%±0.17 (w/w). The cumulative release of OMVs-MSN-5-FU reached 75.07%±0.94 in tumour microenvironment. The percentage of cell viability of OMVs-MSN-5-FU was 33.75%±2.73. In vivo experiments results confirmed that OMVs-MSN-5-FU could be taken up by colon cancer cells.Conclusions The study provided a promising nano platform for the targeting treatment of colon cancer.
研究领域:
药理学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Nature Protocols
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2022
·Vol. 17
·期 10
·2240-2274
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IF 17.021
Zhao Xiao,Zhao Ruifang,Nie Guangjun
Here we present a protocol for the construction and use of two types of nanocarrier based on bacterial membrane materials for cancer vaccine delivery. Cancer vaccines induce tumor regression through triggering the specific T-cell responses against tumor neoantigens, a process that can be enhanced by nanocarrier delivery. Inspired by the body’s natural immune defenses against bacterial invasion, we have developed two different types of nanocarrier based on bacterial membrane materials, which employ genetically engineered outer-membrane vesicles (OMVs), or hybrid membrane vesicles containing bacterial cytoplasmic membrane, respectively. The OMV-based nanocarriers can rapidly display different tumor antigens through the surface modified Plug-and-Display system, suitable for customized cancer vaccines when the tumor neoantigens can be identified. The hybrid membrane-based nanocarriers are prepared through fusion of the bacterial cytoplasmic membrane and the primary tumor cell membrane from surgically removed tumor tissues, possessing unique advantages as personalized cancer vaccines when the neoantigens are not readily available. Compared with chemically synthesized nanocarriers such as liposomes and polymer without intrinsic adjuvant properties, owing to the large amounts of pathogen-associated molecular patterns, the two nanocarriers can activate the antigen-presenting cells while delivering multiple antigens, thus inducing effective antigen presentation and robust adaptive immune activation. Excluding bacterial culture and tumor tissue collection, the preparation of OMV- and hybrid membrane-based nanocarriers takes ~8 h and 10 h for tumor vaccine construction, respectively. We also detail how to use these nanocarriers to create cancer nanovaccines and evaluate their immunostimulatory and antitumor effects.
研究领域:
癌症免疫治疗
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纳米技术
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生物医学工程
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免疫学
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DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2024
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IF 2.7
Xinyu Wang,Hui Zhang,Ping Bai,Jinjin Shi,Qiaoyun Li,Wei Liu
Inhibition of protein neddylation pathway has emerged an attractive anticancer strategy in pre-clinical studies. MLN4924, as a small molecule inhibitor of the neddylation, has been found to effectively inhibit the growth of a variety of cancer cells. However, its clinical application still faces some major challenges in terms of the poor water solubility, biological stability, poor targeting, and rapid clearance from the body. Herein, we developed a biomimetic nanovesicle platform (named P-PAM/MLN) by ultrasonically storing MLN4924-loaded polyamidoamine (PAMAM) dendrimer into platelet membrane vesicles (PMVs) for tumor therapy. Benefiting from PMVs-based camouflage, P-PAM/MLN exhibited enhanced tumor affinity, avoiding the off-target toxicity of MLN4924. Moreover, P-PAM/MLN could selectively release MLN4924 in response to the acidic microenvironment of lysosomal compartments via "Proton Sponge" effect. Conse-quently, the biomimetic nanovesicles could remarkably inhibit tumor progression with negligible toxicity. In terms of significance, the nanovesicles provide a precisely targeted delivery platform for delivering small molecule drugs to the tumor tissue as well as an effective reference for the combined application of nanocarriers and clinical drugs.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Wen-Ba Wang,Jia-Yang Wan,Dao-Jun Yu,Hai-Xia Du,Hui-Fen Zhou,Hai-Tong Wan,Jie-Hong Yang
Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKp) infection poses a significant global public health challenge, with the misuse of antibiotics further contributing to the development of resistance and triggering harmful inflammatory responses. Outer membrane vesicles (OMVs) released by CRKp under sub-lethal concentration of MEM pressure (KOMV-MEM) exhibit enhanced virulence and greater efficiency in transferring resistance genes.Methods: We investigated the inhibitory effects of chlorogenic acid (CA) on KOMV-MEM characteristics and its protective role in KOMV-MEM infected mice. Based on LC-MS proteomic analysis of vesicles, we screened for potential targets of KOMV-MEM in promoting macrophage (MØ) pyroptosis pathways and inducing resistance gene transfer. Subsequently, computational predictions and experimental validation were performed to determine how CA regulates these mechanisms.Results: This study confirmed that, under MEM pressure, the exacerbated infection levels in CRKp-inoculated mice are attributable to the high virulence of KOMV-MEM. Computational and experimental results demonstrated that CA inhibits pyroptosis by reducing MØ capture of KOMV-MEM through blocking the interaction between GroEL and LOX-1. Furthermore, CA prevents the spread of resistance genes by disrupting the conjugation and transfer processes between KOMV-MEM and recipient bacteria. Finally, in vitro and in vivo assays showed that CA inhibits KOMV-MEM resistance enzymes, thereby preventing the hydrolysis of MEM in the environment and depriving susceptible bacteria of protection.Discussion: These findings provide the first confirmation that CA can inhibit both the virulence and the transmission of drug resistance in KOMV-MEM. This underscores the potential of CA treatment as a promising antimicrobial strategy against CRKp infection.
研究领域:
微生物学
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药理学
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感染与免疫
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DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-14
·
IF 15.7
Gong Xu,Liu Shan,Xia Bozhang,Wan Yichen,Zhang Shuyi,Zhang Baoyan,Wang Zehao,Chen Junge,Xiao Fei,Liang Xing-Jie,Yang Yun
Genetically engineered commensal bacteria are promising living drugs, however, their therapeutic molecules are frequently confined to their colonization sites. Herein, we report an oral protein delivery technology utilizing an engineered bacterial type zero secretion system (T0SS) via outer membrane vesicles (OMVs). We find that OMVs produced in situ by Escherichia coli Nissle 1917 (EcN) can penetrate the intact gut epithelial barrier to enter the circulation and that epithelial transcytosis involves pinocytosis and dynamin-dependent pathways. EcN is engineered to endogenously load various enzymes into OMVs, and the secreted enzyme-loaded OMVs are able to stably catalyze diverse detoxification reactions against digestive fluid and even enter the circulation. Using hyperuricemic mice and uricase delivery as a demonstration, we demonstrate that the therapeutic efficacy of our engineered EcN with a modified T0SS outperforms that with a direct protein secretion apparatus. The enzyme-loaded OMVs also effectively detoxify human serum samples, highlighting the potential for the clinical treatment of metabolic disorders.
研究领域:
分子生物学
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医学工程
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微生物学
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DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 12
·
IF 11.7
Xianyuan Wei,Bin Xue,Shuangchen Ruan,Jintong Guo,Yujing Huang,Xiaorui Geng,Dan Wang,Cangtao Zhou,Jun Zheng,Zhen Yuan
To eliminate multidrug-resistant bacteria of Acinetobacter baumannii, we screened 1100 Food and Drug Administration–approved small molecule drugs and accessed the broxyquinoline (Bq) efficacy in combination with various metal ions. Antibacterial tests demonstrated that the prepared Zn(Bq)2 complex showed ultralow minimum inhibitory concentration of ~0.21 micrograms per milliliter with no resistance after 30 passages. We then constructed the nano zeolitic imidazolate framework-8 (ZIF-8) as a drug carrier of Zn(Bq)2 and also incorporated the photosensitizer chlorin e6 (Ce6) to trace and boost the antibacterial effect. To further ensure the stable and targeted delivery, we genetically engineered outer membrane vesicles (OMVs) with the ability to selectively target A. baumannii. By coating the ZnBq/Ce6@ZIF-8 core with these OMV, the resulted drug (ZnBq/Ce6@ZIF-8@OMV) exhibited exceptional killing efficacy (>99.9999999%) of A. baumannii. In addition, in vitro and in vivo tests were also respectively carried out to inspect the remarkable efficacy of this previously unknown nanodrug in eradicating A. baumannii infections, including biofilms and meningitis.
研究领域:
微生物学
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Wenfei Chen,Yuanshuai Song,Shuting Bai,Chunting He,Zhaofei Guo,Yining Zhu,Zhirong Zhang,Xun Sun
As adjuvants or antigens, bacterial membranes have been widely used in recent antibacterial and antitumor research, but they are often injected multiple times to achieve therapeutic outcomes, with limitations in biosafety and clinical application. Herein, we leverage the biocompatibility and immune activation capacity of Salmonella strain VNP20009 to produce double-layered membrane vesicles (DMVs) for enhanced systemic safety and antitumor immunity. Considering the photothermal effect of polydopamine upon irradiation, VNP20009-derived DMVs are prepared to coat the surface of mesoporous polydopamine (MPD) nanoparticles, leading to the potential synergies between photothermal therapy mediated by MPD and immunotherapy magnified by DMVs. The single dose of MPD@DMV can passively target tumors and activate the immune system with upregulated T cell infiltration and secretion levels of pro-inflammatory factors as well as antitumor related cytokines. All of these promoted immune responses result in malignant melanoma tumor regression and extended survival time on local or distant tumor-bearing mouse models. Importantly, we further explore the advantages of intravenous injection of the MPD@DMV agent compared with its intratumoral injection, and the former demonstrates better long-term immune effects on animal bodies. Overall, this formulation design brings broader prospects for the autologous vaccine adjuvant by bacterial membrane vesicles in cancer therapy.
研究领域:
癌症研究
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纳米技术
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免疫学
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药学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-20
·
IF 15.7
Dong Huijun,Pan Zihang,Jiao Pengtao,Ye Fei,Peng Qi,Yu Yanying,Lai Xinyuan,Li Huan,Guan Zhao,Deng Juan,Shen Tao,Tan Wenjie,Shi Yi,Ding Qiang,Luo Jianyuan,Li Tong,Zhuang Hui,Xiang Kuanhui
Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.
研究领域:
细胞生物学
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病毒学
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分子生物学
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发育生物学
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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）