bims-engexo 2025-07-27 papers

Invest New Drugs. 2025 Jul 24.

Comparative analysis of engineered-exosome delivered si-HER2 and trastuzumab in the treatment of HER2-positive gastric cancer.

Yuehong Zhu, Yaoyang Guo, Ziyi Dong, Mingqing Zhang, Hui Liu, Xinyi Wen, Wenwen Pang, Xipeng Zhang, Zhansheng Jiang, Chong Chen, Jie Hao, Ming Gao, Haiyang Zhang.

Trastuzumab is currently a key targeted drug for HER2-positive gastric cancer (GC), but there are common problems of drug resistance and cardiotoxicity in clinical treatment, resulting in poor therapeutic effects. Exosomes are natural nanocarriers for drug delivery and engineered exosomes have been widely used in translational medicine research. This study is designed to compare the anti-tumor effects and adverse effects between engineered exosomes carrying HER2 siRNA and trastuzumab. The stable cell line of iRGD-293T was constructed by using lentiviruses, and iRGD-293T and 293T cells were transfected with si-HER2 and exosomes were isolated by ultra-centrifugation. Functional experiments were performed to examine the inhibitory effects of iRGD-exo-si-HER2 and trastuzumab on both HER2-positive GC cells and mouse xenograft models. Blood biochemical indexes were used to test the adverse effects, especially cardiotoxicity. The engineered exosomes modified by iRGD peptide showed higher tumor affinity compared to control exosomes in vitro and in vivo. si-HER2 delivered by iRGD-exosomes significantly inhibited the proliferation and promoted apoptosis of HER2-positive GC cells, and iRGD-exo-si-HER2 significantly reduced the expression of HER2 in GC cells in vitro and in vivo, showing similar efficacy as trastuzumab but with lower cardiac side effects. Our data indicated that iRGD-exo-si-HER2 shows good anti-tumor effect both in vivo and in vitro, and has fewer side effects compared with trastuzumab. And this study suggested that engineering exosomes with si-HER2 can serve as novel strategy for the treatment of HER2-positive GC.

Keywords: Engineered exosomes; HER2; Trastuzumab; iRGD; siRNA

DOI: https://doi.org/10.1007/s10637-025-01558-z

Acta Biomater. 2025 Jul 18. pii: S1742-7061(25)00537-9. [Epub ahead of print]

Engineered M2 Macrophage-Derived Exosomes: Mechanisms and Therapeutic Potential in Inflammation Regulation and Regenerative Medicine.

Xuan Guan, Chengyu Li, Xinyi Wang, Liqing Yang, Yao Lu, Zehong Guo.

M2 macrophage-derived exosomes (M2-Exos) are nanoscale vesicles enriched with bioactive cargo inherited from their parent M2 macrophages. Although M2-Exos emerge as a promising therapeutic agent due to their dual capacity of immunomodulation and tissue repair, they face critical limitations in applications, including low targeting specificity, cargo-loading capacity, and stability. Therefore, strategies are needed to construct engineered M2-Exos for enhancing therapeutic efficacy. In this review, we will first provide an overview of M2-Exos, including the preparation processes, parent cell sources, characterization, and delivery system. Second, we will examine advanced engineering approaches applied to M2-Exos, focusing on the enhancement of M2-Exos in terms of targeting specificity, payload retention, and microenvironment-responsive release kinetics. Third, we will introduce current applications of the engineered M2-Exos in the inflammatory diseases and regenerative medicine. The roles and the underlying therapeutic mechanisms of engineered M2-Exos in controlling inflammation and tissue regeneration are also discussed. Finally, we will also highlight the challenges in translating M2-Exos from bench to bedside, alongside perspectives for overcoming these barriers. By bridging mechanistic insights with emerging bioengineering technologies, future breakthroughs will unlock the full potential of engineered M2-Exos across precision therapy and cell-free tissue engineering. STATEMENT OF SIGNIFICANCE: M2 macrophage derived exosomes (M2-Exos) provide cell-free alternatives in regenerative medicine and immune regulation by utilizing the ability of M2 macrophages to regulate immune responses and coordinate tissue repair, yet their clinical translation is hindered by inherent limitations. Addressing these challenges through bioengineering strategies is critical to amplify their therapeutic efficacy and broaden clinical applicability. Recent advances in surface modification, cargo encapsulation, and stimulus-responsive delivery systems have significantly improved M2-Exos' targeting specificity, payload capacity, and controllability, making them precision tools for inflammatory diseases and regenerative medicine. This review not only provides a comprehensive framework for engineering M2-Exos but also offers insights into their mechanisms in resolving inflammation and promoting tissue repair.

Keywords: Biomaterials; Exosomes; Inflammation; M2 macrophage; Tissue engineering

DOI: https://doi.org/10.1016/j.actbio.2025.07.039

Immunobiology. 2025 Jul 16. pii: S0171-2985(25)00237-2. [Epub ahead of print]230(4): 153103

Exosomes derived from baicalin-pretreated bone marrow mesenchymal stem cells inactivate the TLR4/MyD88/NF-kB pathway to improve asthma.

Wenbo Shen, Wei Jia, Qiang Wu, Li Shen, Yisheng Wang.

BACKGROUND: Baicalin, a natural compound isolated from the root of Scutellaria baicalensis Georgi, has been shown to have various pharmacological effects on lung diseases including asthma. Recently, research has suggested that baicalin combined with exosomes may have significant potential against disease development. The present work analyzes the effects of exosomes derived from baicalin-pretreated bone marrow mesenchymal stem cells (BMSCs) on asthma and the underlying mechanism.
METHODS: BALB/c mice were sensitized with ovalbumin (OVA) through intraperitoneal injection to establish an animal model of asthma. Human bronchial epithelial cells (16HBE) were exposed to lipopolysaccharide to mimic a cell model of asthma. The pathological conditions of lung tissues in OVA-induced mice were analyzed by haematoxylin and eosin staining assays. Masson staining and quantification analysis were conducted to analyze percentage of collagen fibers in lung tissues of OVA-induced mice. The Wright-Giemsa assay was used to determine the number of eosinophils, neutrophils, lymphocytes and macrophages. Enzyme-linked immunosorbent assays were performed to analyze expression levels of inflammatory factors including IL-4, IL-5, IL-13 and TNF-α levels. The values of airway resistance (Rrs), elastance (Ers) and compliance (Crs) were recorded for analyzing airway hyperresponsiveness through the FlexiVent system. Protein expression was analyzed by immunohistochemistry (IHC) and/or western blotting assay.
RESULTS: Ovalbumin (OVA) pretreatment increased airway inflammation, airway hyperresponsiveness, collagen deposition and epithelial-mesenchymal transition (EMT) in mice, however, these phenomena were significantly improved after treatment with baicalin-pretreated BMSC exosomes. Lipopolysaccharide (LPS)-induced 16HBE cells showed increased levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13) and tumor necrosis factor-α (TNF-α), elevated N-cadherin and Vimentin protein expression, and decreased E-cadherin protein expression, whereas these LPS-induced effects were relieved after treatment with baicalin-pretreated BMSC exosomes. Additionally, protein expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88) and phosphor p65 (p-p65) was upregulated in lung tissues of OVA-induced mice and LPS-stimulated 16HBE cells, but these phenomena were counteracted following exosomes treatment from baicalin-pretreated BMSCs.
CONCLUSION: Exosomes derived from baicalin-pretreated BMSCs ameliorated airway inflammation, airway hyperresponsiveness and airway remodeling after asthma by inactivating the TLR4/MyD88/nuclear factor kappa B pathway, providing a therapeutic strategy for asthma.

Keywords: Asthma; Baicalin; Bone marrow mesenchymal stem cells; Exosomes

DOI: https://doi.org/10.1016/j.imbio.2025.153103

J Natl Cancer Cent. 2025 Jun;5(3): 252-266

The role of exosomes in bladder cancer immunotherapy.

Mohammad Mousaei Ghasroldasht, Piyush K Agarwal.

Bladder cancer remains a significant global health challenge, requiring repeated treatments and surveillance and potentially morbid therapies, particularly in advanced and recurrent stages. Exosomes, small extracellular vesicles central to intercellular communication, have emerged as innovative tools in cancer diagnostics, prognosis, and therapy. Their role in modulating the immune response and the tumor microenvironment makes them particularly attractive for cancer immunotherapy. This review provides a comprehensive overview of exosome biology, with a focus on their role in immune modulation and potential therapeutic applications. We explore the progress and challenges of exosome-based immunotherapy in cancer, followed by a discussion on the current state of bladder cancer immunotherapy. Additionally, we highlight the roles of exosomes in bladder cancer, emphasizing their diagnostic and prognostic applications. Despite promising preclinical studies and a growing number of clinical trials in other cancers, exosome-based therapies remain underexplored in bladder cancer. We discuss the current clinical trials related to exosomes in bladder cancer and propose their potential future role in immunotherapy. Finally, we address the challenges and opportunities in translating exosome-based therapies from bench to bedside, emphasizing the need for further preclinical and clinical investigations. This review emphasized the potential of exosome-based immunotherapy as a transformative approach for bladder cancer diagnosis and treatment.

Keywords: Bladder cancer; Cancer immunotherapy; Exosome; Exosome based immunotherapy

DOI: https://doi.org/10.1016/j.jncc.2025.04.001

Front Immunol. 2025 ;16 1567167

miR-107-enriched exosomes promote ROS/wnt/autophagy, inhibit intracellular mycobacterial growth and attenuate lung infection.

Wei Xu, Yuan Wu, Min Yang, Jiayu Zhou, Liying Zhu, Xiaosai Ma, Chonghai Qiu, Ling Shen, Hongbo Shen, Feifei Wang.

Exosomes, known as small membrane vesicles of endocytic origin produced by most cell types, exist in a variety of body fluids including plasma. The roles of exosomes in immune responses against Mycobacteria tuberculosis (Mtb) infection remain poorly characterized. Here, we found that miR-107 highly expressed in exosomes from plasma of TB patients but not healthy control (HC) subjects. Consistently, such miR-107-high exosomes were also detected in both the extracellular fluid released by mycobacterial-infected macrophages and the plasma of mycobacterial-infected mice. Interestingly, adding the miR-107-high plasma exosomes or the miR-107 mimics to infected THP-1 macrophages inhibited intracellular mycobacterial growth. Consistently, while nanoscale and fluorescence imaging revealed that miR-107 could be transferred inter-cellularly via exosomes, miR-107-enriched exosomes from miR-107 overexpressing cells also inhibited mycobacterial growth in THP-1 macrophages and primary monocytes/peripheral blood mononuclear cells (PBMC). Mechanistically, miR-107-high exosomes increased ROS production; miR-107 regulated Wnt pathway by targeting Wnt16 and promoted autophagy in THP-1 macrophages. Furthermore, treatment of infected mice with miR-107-enriched exosomes reduced mycobacterial infection in lung tissues. Our results raise a possibility to explore miR-107-high plasma exosomes for a potential surrogate marker for TB. Findings suggest that exosomes enriched with miR-107 or other bio-active molecules may potentially serve as an attractive approach for treatment of infection.

Keywords: ROS; Wnt; miR-107; mycobacteria tuberculosis; plasma exosomes

DOI: https://doi.org/10.3389/fimmu.2025.1567167

Sci Rep. 2025 Jul 18. 15(1): 26138

Prostate cancer cell-derived exosomes inhibit macrophage phagocytosis through EIF3B-mediated exosomal sorting of miR-100-5p.

Yanyan Zhang, Yinying Hu, Hongyan Guo, Min Zhao, Shiqi Liu, Jing Liu, Yanqin Huang, Zhigang Wang.

Exosomes play significant roles in the tumor microenvironment (TME). In particular, some exosomal microRNAs (miRNAs) have the ability to mediate macrophage polarization. However, the mechanism underlying the selective enrichment of miRNAs into exosomes remains largely unknown. Herein, we compared the expression of miR-100-5p in exosomes derived from normal prostate epithelial cells and PC-3 cells. Subsequently, macrophages were treated with the aforementioned exosomes separately. Our results demonstrate that prostate cancer (PC)-derived exosomes can transfer miRNA-100-5p to macrophages and significantly increase miR-100-5p expression. To explore the role and mechanisms of exosomal miR-100-5p in macrophages, we performed phagocytosis assay and reactive oxygen species (ROS) detection experiment. Knockdown of miR-100-5p markedly promoted ROS generation in macrophages induced with PC-3 exosomes through the NADPH oxidase 4 (NOX4) pathway, leading to the increased phagocytosis of macrophages. Importantly, our results confirmed that eukaryotic translation initiation factor 3 subunit B (EIF3B) was highly expressed in PC cells and specifically bound to miR-100-5p by pull-down assay, and EIF3B knockdown decreased the enrichment of miR-100-5p in PC-3 exosomes. Collectively, our data showed that EIF3B-mediated selective sorting of miR-100-5p into PC exosomes reduced the generation of ROS by targeting NOX4 in macrophages, thus inhibiting macrophage phagocytosis. These findings reveal a new role for EIF3B in regulating the sorting of miR-100-5p into PC-3-derived exosomes, and identify an important new mode of TME regulation.

Keywords: EIF3B; Exosome; Macrophage; Prostate cancer; miRNA-100-5p

DOI: https://doi.org/10.1038/s41598-025-11799-w