Research on extracellular vesicles including exosomes, microvesicles, and their roles in intercellular communication and disease

Extracellular Vesicles in Cancer Therapy

Extracellular vesicles (EVs) have emerged as pivotal players in cancer therapy, particularly in enhancing the efficacy of immunotherapeutic strategies. One notable study developed a heterogenic fusion membrane tumor vaccine, EV-CM, which combines extracellular vesicles from Staphylococcus aureus with tumor cell membranes from B16F10 melanoma cells. This innovative approach demonstrated significant immune-boosting effects, suggesting that the fusion of different EV sources can enhance therapeutic outcomes (ref: Guo doi.org/10.1038/s41392-025-02355-z/). Another study focused on the delivery of SOD1-siRNA encapsulated in small EVs, targeting spinal neurons in a transgenic mouse model of amyotrophic lateral sclerosis. This method resulted in a marked reduction of mutant SOD1 protein levels and significant symptom amelioration, showcasing the potential of engineered EVs in gene therapy applications (ref: Guo doi.org/10.1093/brain/). Furthermore, targeting Reticulin 4 within small EVs was shown to combat metastasis and enhance immunotherapy in triple-negative breast cancer, indicating that specific cargo within EVs can be harnessed for therapeutic benefits (ref: Wang doi.org/10.1002/jev2.70154/). Overall, these studies highlight the versatility of EVs in cancer therapy, from vaccine development to gene silencing and targeted treatment strategies. In addition to these therapeutic applications, advancements in detection methods for EVs are crucial for their clinical utility. A study introduced a time-gated luminescence resonance energy transfer strategy using near-infrared long lifetime upconversion nanoparticles, achieving an eight-fold increase in luminescence lifetime for microRNA detection. This enhanced sensitivity could facilitate the identification of specific EVs associated with cancer progression (ref: Kim doi.org/10.1038/s41467-025-62802-x/). Another innovative approach involved conductive microneedles loaded with polyphenol-engineered exosomes, which effectively reshaped diabetic neurovascular niches, demonstrating the potential of EVs in chronic wound healing (ref: Liu doi.org/10.1002/advs.202507974/). Collectively, these findings underscore the multifaceted roles of EVs in cancer therapy, ranging from direct therapeutic applications to novel detection methodologies.

Extracellular Vesicles in Immune Modulation

Extracellular vesicles (EVs) play a critical role in immune modulation, influencing both innate and adaptive immune responses. A significant advancement in this field is the development of a magnetic nanochains platform for N-glycoproteomic analysis of EVs, which enables the capture and enrichment of glycoproteins from ultratrace biofluids. This platform addresses the analytical challenges posed by the low abundance of EVs and holds promise for liquid biopsy applications (ref: Li doi.org/10.1038/s41467-025-63075-0/). Additionally, the study of bacterial EVs has revealed their role in horizontal gene transfer, enhancing microbial adaptability. This research highlights the mechanisms by which specific gene clusters are enriched in bacterial EVs, providing insights into their evolutionary significance (ref: Takano doi.org/10.1093/ismejo/). Moreover, the therapeutic potential of EVs in cancer treatment has been explored through the delivery of circRNA, specifically hsa_circp53_0041947, which demonstrated anti-cancer effects by activating the CypD/TRAP/HSP90 pathway. This approach offers a novel strategy for targeting malignancies with high-risk genetic mutations (ref: Yu doi.org/10.1038/s12276-025-01506-0/). In the context of immunotherapy, an avidity-based capture strategy for PD-L1-expressing exosomes was developed, enhancing the prediction of patient responses to immunotherapy. This method leverages dendrimer-mediated multivalent binding to improve the sensitivity and specificity of exosome detection (ref: Lee doi.org/10.1002/advs.202509270/). Collectively, these studies illustrate the diverse roles of EVs in immune modulation, from enhancing therapeutic efficacy to serving as biomarkers for disease progression.

Extracellular Vesicles in Neurological Disorders

Extracellular vesicles (EVs) are increasingly recognized for their potential in treating neurological disorders, particularly in neuroprotection and vascular repair. A study investigated the effects of intravenously injected human pluripotent stem cell-derived pericytes and their EVs in a mouse model of Alzheimer's disease. The findings indicated that these EVs play a crucial role in neuroprotection and promoting vascular repair, highlighting their therapeutic potential in neurodegenerative diseases (ref: Liu doi.org/10.1016/j.ymthe.2025.08.024/). Additionally, the role of α-synuclein in promoting neurofilament light chain release from oligodendrocytes was examined, revealing that increased α-synuclein levels correlate with elevated neurofilament expression in multiple system atrophy patients, suggesting a potential biomarker for disease progression (ref: Zheng doi.org/10.1002/ana.70029/). Moreover, the design of agonists to tune granulocyte-colony-stimulating factor receptor (G-CSFR) signaling has emerged as a novel approach to enhance cytokine-based therapies for neurological conditions. By systematically varying receptor-binding affinity and dimerization geometry, researchers aim to improve therapeutic outcomes in hematopoietic stem cell differentiation (ref: Ullrich doi.org/10.1016/j.ymthe.2025.08.031/). These studies collectively underscore the importance of EVs in neurological disorders, not only as therapeutic agents but also as potential biomarkers for disease monitoring and progression.

Extracellular Vesicles in Cardiovascular Research

Extracellular vesicles (EVs) are gaining recognition for their roles in cardiovascular research, particularly in understanding angiogenesis and vascular remodeling. A study isolated EVs from mouse tumor tissues, demonstrating their ability to induce angiogenesis through VEGF production from macrophages. This finding highlights the potential of tumor-derived EVs in mediating vascular changes associated with cancer progression (ref: Yoon doi.org/10.1002/jev2.70138/). Furthermore, exomeres derived from adventitial fibroblasts of spontaneously hypertensive rats were shown to promote vascular remodeling by transferring osteopontin, indicating a significant role of EVs in hypertension-related vascular changes (ref: Wang doi.org/10.1002/jev2.70146/). In addition to these findings, a novel nanophotonic biosensor system was developed to visualize single-exosome dynamics within the gut-brain axis, enabling real-time observation of exosome interactions in a microfluidic environment. This innovative approach provides insights into the biochemical communication between the gastrointestinal tract and the central nervous system, which is crucial for understanding cardiovascular health (ref: Lee doi.org/10.1021/acsnano.5c09164/). These studies collectively emphasize the multifaceted roles of EVs in cardiovascular research, from mediating angiogenesis to facilitating inter-organ communication.

Extracellular Vesicles in Metabolic Regulation

Extracellular vesicles (EVs) are increasingly recognized for their role in metabolic regulation, particularly in cancer progression and pain management. A study revealed that TERC, a non-coding RNA, stimulates fatty acid metabolism, promoting bladder cancer growth and invasion. Elevated levels of TERC in urine and plasma exosomes were associated with lymph node metastasis and larger tumor size, suggesting its potential as a biomarker for urothelial carcinoma (ref: Chen doi.org/10.1158/0008-5472.CAN-24-3439/). Additionally, mesenchymal stem cell-derived EVs preconditioned with tumor necrosis factor-α demonstrated enhanced analgesic efficacy in a neuropathic pain model, indicating their therapeutic potential in pain management (ref: Zhang doi.org/10.1016/j.bioactmat.2025.07.029/). Moreover, the mechanisms underlying TLR4 maturation were explored, revealing that loss of CCDC134 leads to retention of TLR4 in the endoplasmic reticulum, thus blocking its maturation. This study highlights the importance of EVs in maintaining immune homeostasis and their potential implications in metabolic disorders (ref: Bai doi.org/10.1073/pnas.2512154122/). Collectively, these findings underscore the critical roles of EVs in metabolic regulation, from influencing cancer metabolism to modulating pain responses.

Extracellular Vesicles in Infectious Diseases

Extracellular vesicles (EVs) are emerging as critical components in the study of infectious diseases, particularly in their role in immune responses and pathogen interactions. A study focused on the macrophage response to Mycobacterium tuberculosis, revealing that EVs secreted by infected macrophages play a significant role in combating the infection. This research provides insights into the immune mechanisms and the potential of EVs as therapeutic agents against tuberculosis (ref: Yang doi.org/10.1093/gpbjnl/). Additionally, the biogenesis of outer-inner membrane vesicles induced by X-ray irradiation of Pseudomonas aeruginosa was investigated, suggesting their potential as a vaccine against acute pneumonia (ref: Zhang doi.org/10.1002/jev2.70151/). Furthermore, the genetic architecture of hypertrophic cardiomyopathy was redefined, highlighting the role of intermediate-effect variants in modulating disease expression. This study emphasizes the importance of understanding the genetic factors that contribute to infectious disease susceptibility and progression (ref: García Hernandez doi.org/10.1161/CIRCULATIONAHA.125.074529/). Collectively, these studies illustrate the multifaceted roles of EVs in infectious diseases, from mediating immune responses to serving as potential therapeutic agents.

Extracellular Vesicles in Regenerative Medicine

Extracellular vesicles (EVs) are increasingly recognized for their potential in regenerative medicine, particularly in enhancing tissue repair and regeneration. A study developed a multidimensional engineering strategy for EVs, termed C-A/R-EVs, aimed at targeted delivery and microglial reprogramming in spinal cord injury repair. This approach demonstrated synergistic therapeutic potential, addressing the challenges of low bioactivity and targeting efficiency of natural EVs (ref: Xiong doi.org/10.1021/acsnano.5c08573/). Additionally, pericytes were shown to promote metastasis by regulating local vascular tone and hemodynamics, indicating their role in tumor progression and the potential of targeting EVs for therapeutic interventions (ref: Li doi.org/10.1038/s41467-025-62475-6/). Moreover, the delivery of circRNA via EVs was explored as a novel therapeutic strategy for multiple cancers, demonstrating anti-cancer effects through the activation of the CypD/TRAP/HSP90 pathway. This highlights the potential of EVs in delivering RNA-based therapeutics for cancer treatment (ref: Yu doi.org/10.1038/s12276-025-01506-0/). Collectively, these findings underscore the transformative potential of EVs in regenerative medicine, from enhancing tissue repair to delivering targeted therapies.

Extracellular Vesicles in Biomarker Discovery

Extracellular vesicles (EVs) are gaining traction as valuable sources for biomarker discovery due to their role in mediating intercellular communication and disease progression. A study developed a magnetic nanochains platform for N-glycoproteomic analysis of EVs, enabling the capture and enrichment of glycoproteins from ultratrace biofluids. This innovative approach addresses the challenges of low EV abundance and holds promise for liquid biopsy applications (ref: Li doi.org/10.1038/s41467-025-63075-0/). Additionally, the enrichment of horizontally transferred gene clusters in bacterial EVs was investigated, shedding light on their role in microbial adaptability and potential evolutionary implications (ref: Takano doi.org/10.1093/ismejo/). Furthermore, EVs derived from Lactobacillus rhamnosus GG were shown to inhibit HSV-2 infection by activating the NOD2-IFN-I signaling pathway, highlighting their potential as therapeutic agents and biomarkers for viral infections (ref: Wang doi.org/10.1002/jev2.70152/). Collectively, these studies illustrate the diverse applications of EVs in biomarker discovery, from identifying disease-specific glycoproteins to exploring their roles in microbial infections.

Key Highlights

Disclaimer: This is an AI-generated summarization. Please refer to the cited articles before making any clinical or scientific decisions.