bims-engexo 2025-08-10 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–08–10
nine papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Brain-Derived Exosomes in Neurodevelopmental and Neuropsychiatric Disorders: Molecular Insights, Therapeutic Potential, and Translational Challenges.
Prospective effect of mesenchymal exosomes versus nanocurcumin-loaded mesenchymal exosomes on induced periodontitis in albino rats.
Advancements in exosome-based cancer diagnosis: from chipsets to nano vaccine.
Exosomes in ovarian cancer: Impact on drug resistance and advances in SERS detection techniques.
Glyphosate targets FYN to regulate glycolysis and promote glioblastoma proliferation: A network toxicology study.
NK-derived exosomes in anti-tumor strategies.
Adipose Mesenchymal Stem Cell-Derived Exosomes in Conjunction with Roflumilast Ameliorate Chronic Kidney Disease Through the Modulation of Fibrosis and Inflammation.
Exosome Therapy: A Promising Avenue for Treating Intervertebral Disc Degeneration.
An electrospun membrane incorporating lipocalin 2-enhanced exosomes effectively facilitated the repair of critical bone defects.

Mol Neurobiol. 2025 Aug 02.

Brain-Derived Exosomes in Neurodevelopmental and Neuropsychiatric Disorders: Molecular Insights, Therapeutic Potential, and Translational Challenges.

Masoud Nikanfar, Cigir Biray Avci, Asghar Khalilnezhad, Elham Shahriyari, Alireza Nourazarian.

  Neurodevelopmental disorders (NDDs), including autism spectrum disorders, attention-deficit hyperactivity disorders, schizophrenia, bipolar disorders, and other neurological disorders, present significant diagnostic and therapeutic challenges due to complex pathological physiology and heterogeneous presentation. Brain-derived exosomes, which are extracellular vesicles measuring 30-150 nm, cross the blood-brain barrier, transporting disease-specific molecular cargoes such as proteins, lipids, and nucleic acids, making them promising biomarkers and therapeutic vehicles. Recent advances have identified exosomal features specific to the disorder, including a reduction in brain-derived neurotrophic factors and an increase in miR-125b in ADHD, an increase in miR-146a and IL-6 in autism spectrum disorders, a change in sphingolipid profiles in schizophrenia, and a dysregulation of phosphatidylserine in bipolar disorders. These molecular signatures enable noninvasive surveillance of disease progression and response. BDEs exhibit context-dependent functions and can be both neuroprotective and potential agents for disease spread, depending on the cellular microenvironment. Important translational barriers include standardizing isolation methods, scaling up clinical production, and developing regulatory frameworks. Current evidence supports progress in clinical trials and continues to investigate manufacturing standards and therapeutic dosage protocols for these agents. Brain-derived exosome represents a convergence of neuroscience and precision medicine, providing pathways for improving the diagnosis and customized treatment strategies for NDD.

Keywords:  Biomarkers; Brain-derived exosomes; Extracellular vesicles; Neurodevelopmental disorders; Neuropsychiatric disorders; Personalized medicine; Therapeutics

DOI:  https://doi.org/10.1007/s12035-025-05247-z
Odontology. 2025 Aug 03.

Prospective effect of mesenchymal exosomes versus nanocurcumin-loaded mesenchymal exosomes on induced periodontitis in albino rats.

Nehad M Abd-Elmonsif, Sherif Gamal, Mona El Deeb, Amany A Rabea.

  Provide insights on the effect of mesenchymal exosomes and Nanocurcumin (NCUR)-loaded exosomes on periodontitis. To induce periodontitis, 42 rats were injected with 3 µL of a 10 mg/mL lipopolysaccharide (LPS) for 4 weeks and divided into 3 categories: untreated Periodontitis, Exosomes treated (single dose 200 µg exosomes), and exosomes loaded NCUR treated group (200 µg exosomes loaded with 200 µg NCUR). In addition, 14 rats were injected PBS to serve as control. Rats were sacrificed between 2 and 4 weeks. Rats were allocated in 7 groups; (Group I (Control), Group II (Periodontitis 2 weeks), Group III (Periodontitis + exosomes 2 weeks), Group IV (Periodontitis + loaded exosomes 2 weeks), Group V (Periodontitis 4 weeks), Group VI (Periodontitis + exosomes 4 weeks) and Group VII (Periodontitis + loaded exosomes 4 weeks). The specimens were prepared for histological, histochemical and ELISA analysis. Histological examination of Group I showed normal structure of periodontium. Groups II and V illustrated reduction in periodontal ligament and different stainability of cementum and bone. Group III revealed disordered periodontal fibers and irregular outlines of cementum and bone. The periodontal fibers in Groups IV and VII were obliquely oriented, and the cementum and bone were consistently stained. Group VI explored dense periodontal ligament. Cementum and alveolar bone showed regular outlines. Masson's trichrome statistical results showed group VI has highest mean. Group V has the greatest IL-1β mean. NCUR-loaded exosomes were found to be more effective in decreasing inflammation and stimulating tissue regeneration in experimental periodontitis.

Keywords:  Exosomes; Nanocurcumin; Nanocurcumin-loaded mesenchymal exosomes; Periodontitis

DOI:  https://doi.org/10.1007/s10266-025-01161-x
Cancer Biol Ther. 2025 Dec;26(1): 2541991

Advancements in exosome-based cancer diagnosis: from chipsets to nano vaccine.

Nobendu Mukerjee, Subham Sarkar, Daniel Ejim Uti, Prashant Kumar Sharma.

  Exosome-based therapies represent a pioneering frontier in cancer treatment, leveraging the natural cellular communication mechanisms encapsulated in exosomes. These nano-sized vesicles serve as carriers of proteins, lipids, and nucleic acids, reflecting the physiological state of their cells of origin, which makes them ideal candidates for targeted cancer therapies and diagnostics. Despite their potential, the path to clinical application is fraught with challenges. This review explores the inherent challenges associated with exosome-based cancer vaccines, focusing on tumor heterogeneity, the technical difficulties in exosome isolation and characterization, the need for standardized protocols, and the scalability of production methods. It also explores the interaction between exosomes and the immune system, a crucial factor in developing effective cancer vaccines. The review explores strategies to improve diagnostic tools, targeted delivery systems, and therapy based on individual tumor profiles, highlighting the need for innovative approaches and collaborative efforts to maximize exosome-based cancer vaccines' therapeutic potential.

Keywords:  Exosomes; cancer nano-vaccines; immune system interaction; lab-on-a-chip; nanotechnology; tumor heterogeneity

DOI:  https://doi.org/10.1080/15384047.2025.2541991
J Pharm Anal. 2025 Jul;15(7): 101170

Exosomes in ovarian cancer: Impact on drug resistance and advances in SERS detection techniques.

Biqing Chen, Xiaohong Qiu, Yang Li.

  Ovarian cancer is a prevalent gynecological malignancy with high mortality and low survival rates. The absence of specific symptoms in early stages often leads to late-stage diagnoses. Standard treatment typically includes surgery followed by platinum and paclitaxel chemotherapy. Exosomes, nanoscale vesicles released by various cell types, are key in intercellular communication, carrying biologically active molecules like proteins, lipids, enzymes, mRNA, and miRNAs. They are involved in tumor microenvironment remodeling, angiogenesis, metastasis, and chemoresistance in ovarian cancer. Emerging research highlights exosomes as drug carriers and therapeutic targets to suppress anti-tumor immune responses. Surface-enhanced Raman scattering (SERS) enables multiplexed, sensitive, and rapid detection of exosome surface proteins, offering advantages such as low background noise, no photobleaching, robustness, and high sensitivity over other detection methods. This review explores the relationship between exosomes and chemoresistance in ovarian cancer, examining the mechanisms by which exosomes contribute to drug resistance and their clinical implications. The goal is to provide new insights into chemoresistance mechanisms, improve diagnosis and intervention strategies, and enhance chemotherapy sensitivity in clinical treatments. In addition, the prospects of exosomes as drug carriers to resist chemical resistance and improve the survival of ovarian cancer patients are summarized. This article emphasizes the role of SERS in detecting ovarian cancer exosomes and advances in exosome detection.

Keywords:  Chemotherapy resistance; Exosomes; Extracellular vesicles; Ovarian cancer; Surface-enhanced Raman scattering (SERS)

DOI:  https://doi.org/10.1016/j.jpha.2024.101170
Int J Biol Macromol. 2025 Jul 31. pii: S0141-8130(25)07043-6. [Epub ahead of print] 146486

Glyphosate targets FYN to regulate glycolysis and promote glioblastoma proliferation: A network toxicology study.

Anquan Ma, Ziqing Yang, Qixuan He, Wenhao Wang, Huiping Ren, Chuanyao Zhai, Jing Lan.

  Environmental glyphosate exposure has been linked to glioblastoma (GBM), yet its molecular basis remains unclear. Integrating network-toxicology and druggable Mendelian randomization screens, we identified the Src-family kinase FYN as the principal glyphosate target. Molecular-dynamics simulations, surface-plasmon resonance (KD = 1.54 μM) and pull-down assays confirmed high-affinity binding and highlighted ASP353 as a dominant contact residue. Multi-omics profiling showed FYN over-expression and promoter hypomethylation in GBM, correlating with diminished immune infiltration. In U87 cells, sub-toxic glyphosate (0.1 mg/L, 12 h) up-regulated FYN, activated PI3K-AKT-mTOR signaling, increased GLUT1, LDHA and PKM2, and accelerated proliferation, migration and invasion; lentiviral sh-FYN reversed these effects and curtailed glycolytic flux. Orthotopic mouse studies mirrored the in-vitro findings, with FYN knock-down suppressing glyphosate-driven tumor growth. Exosomes derived from sh-FYN glioma cells weakened macrophage M2 polarization and reduced CXCL1, IL-10 and TGF-β secretion, revealing an immunometabolism axis. Collectively, these results establish FYN as the mechanistic conduit between glyphosate and GBM and demonstrate that targeting FYN-directly or via exosome delivery-reprograms tumor glycolysis and immunity, offering a tractable strategy against glyphosate-associated malignancy.

Keywords:  FYN; Glioma; Glyphosate

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.146486
Med Oncol. 2025 Aug 09. 42(9): 418

NK-derived exosomes in anti-tumor strategies.

Aohua Zhang, Xiaodi Yin, Jun Ma.

  Tumors remain one of the major challenges confronting researchers today. The development of tumor is driven by genetic factors, environmental exposures, and homeostatic disruptions, leading to the transformation of normal cells into malignant ones. Natural killer (NK) cells, a crucial class of immune cells in immunotherapy, can directly recognize and eliminate tumor cells without prior stimulation by tumor antigens. Exosomes derived from NK cells exert anti-tumor effects through multiple mechanisms, including the release of cytotoxic molecules, death receptor ligand-mediated apoptosis, and the secretion of cytokines and other bioactive molecules. However, the therapeutic efficacy of unmodified exosomes is constrained by insufficient active components, suppression by the tumor microenvironment, and a lack of targeting specificity. Drug loading and engineering strategies can enhance their therapeutic potential. In this review, we examine advancements in NK cell-derived exosome (NK-Exos)-based anti-tumor strategies, focusing on studies involving native exosomes, drug-loaded exosomes, and surface-modified exosomes for tumor eradication.

Keywords:  Cancer; Exosome; Natural killer cell

DOI:  https://doi.org/10.1007/s12032-025-02965-1
Adv Biol (Weinh). 2025 Aug 07. e00152

Adipose Mesenchymal Stem Cell-Derived Exosomes in Conjunction with Roflumilast Ameliorate Chronic Kidney Disease Through the Modulation of Fibrosis and Inflammation.

Mohamed Ali, Mohamed H Sherif, Nashwa Barakat, Bassant Yahia, Ahmed A Shokeir, Basel Sitohy.

  Adipose mesenchymal stem cell-derived exosomes and the PDE4 inhibitor roflumilast (ROF) are investigated as potential treatments for chronic kidney disease (CKD). The exosomes are extracted and analyzed using electron microscopy and flow cytometry, then employed with ROF for in vivo implantation in a CKD animal model. Animals aredivided into seven groups. Group (I) Control; (II) exosomes; (III) ROF; (IV) Adriamycin (ADR); (V) ADR + exosomes, (VI) ADR + ROF, and (VII) ADR + Exosomes+ ROF. Biochemical serum indicators (creatinine, BUN), antioxidant status (GSH, MDA), and the mRNA expressions of TGF-β1, Smad3, IL-6, BAX, Wnt-7, FN, and miRNA145-5p are determined using qRT-PCR. Histology assessment using H&E staining, ultrastructural observation using TEM, and protein expression in kidney tissue (FN1 and BAX) are assessed. The isolated exosomes showed cup-shaped morphologyand expressed CD81, CD9, and CD63. Exosomes and ROF increased glutathione (GSH) levels while decreasing malondialdehyde (MDA) levels. Further, ROF and exosomes treatment lowered the expression of the apoptotic indicators BAX, the fibrotic markers TGFβ1, Smad3, Wnt7a, and FN1, and the inflammatory marker IL6, and increased the expression of miRNA-145. Moreover, ROF and exosomes improved histological and ultrastructural examination. In conclusion, exosomes and ROF can protect against CKD by reducing apoptosis and fibrosis.

Keywords:  adriamycin; chronic kidney disease; exosomes; fibrosis; inflammation; roflumilast

DOI:  https://doi.org/10.1002/adbi.202500152
Tissue Eng Regen Med. 2025 Aug 07.

Exosome Therapy: A Promising Avenue for Treating Intervertebral Disc Degeneration.

Shreya Bhat, Suresh Kannan, Uday Kumar Kolkundkar, Raviraja Neelavar Seetharam.

   BACKGROUND: The human spine relies on intervertebral discs (IVDs) for support and mobility, functioning as shock absorbers that enable friction-free movement. However, IVDs are susceptible to degeneration (IVDD) due to age, excessive strain, and genetic factors, resulting in bulging or herniation that causes pain, stiffness, and nerve compression.
CURRENT TREATMENTS: Current treatments primarily focus on symptom management through medication, physical therapy, or surgery in severe cases, without addressing tissue repair.
EMERGING THERAPIES: Exosome therapy has recently emerged as a promising regenerative approach for IVDD. Exosomes are small, membrane-bound vesicles released by cells, acting as messengers to transport proteins and RNA that influence recipient cell behavior.
POTENTIAL AND CHALLENGES: Researchers are investigating exosomes for IVDD because they may promote disc repair and regeneration by delivering molecules that stimulate tissue recovery and carry anti-inflammatory agents to reduce inflammation and modulate pain. Engineering strategies, such as loading exosomes with therapeutic cargo or targeting molecules, can further enhance their efficacy. While exosome therapy for IVDD is still in early research stages, ongoing studies are promising, though challenges remain in optimizing isolation methods and ensuring clinical safety.
CONCLUSION: Exosome-based therapies could offer a safe, effective, and minimally invasive solution for individuals affected by IVDD.

Keywords:  Exosome therapy; Intervertebral disc degeneration; Nucleus pulposus; Spinal cord injury; Stem cells

DOI:  https://doi.org/10.1007/s13770-025-00746-5
Int J Biol Macromol. 2025 Aug 06. pii: S0141-8130(25)07231-9. [Epub ahead of print] 146674

An electrospun membrane incorporating lipocalin 2-enhanced exosomes effectively facilitated the repair of critical bone defects.

Nanning Lv, Hongye Li, Lihui Hong, Zhonglai Qian, Feng Yuan, Haifu Sun, Mingming Liu.

  The clinical management of critical size bone defects (CSBD) remains a formidable clinical challenge, with no universally efficacious treatment currently established. The intricate interrelationship between bone formation and vascular plasticity constitutes a fundamental prerequisite for successful repair of CSBD. Lipocalin 2 (LCN2), a secretory protein identified within extracellular vesicles derived from osteoblasts, has exhibited notable bone protective properties. In this study, we successfully synthesized a biomimetic electrospun membrane incorporating LCN2-enhanced exosomes, employing polycaprolactone (PCL) as the foundational material, designated PCL/PEI@L-EXO. Cellular treatment with this membrane yielded substantial upregulation of osteogenesis-related genes (Runx2, 11.4-fold; Sp7, 3.0-fold; Bglap, 2.6-fold) alongside pronounced downregulation of adipogenic differentiation-related genes (Klf9, 78.3 %; Leptin, 98.5 %; Pparγ, 86.2 %) relative to the PCL membrane. Transplantation of the PCL/PEI@L-EXO membrane into the cranial defects markedly accelerated the bone healing rate relative to the PCL membrane. Such enhancement manifested through elevated bone volume fraction (BV/TV) (4 weeks, 2.2-fold; 8 weeks, 3.5-fold), augmented trabecular number (TB·N) (4 weeks, 1.2-fold; 8 weeks, 1.3-fold), and enhanced bone mineral density (BMD) (4 weeks, 1.2-fold; 8 weeks, 1.7-fold).

Keywords:  Angiogenesis; Exosomes; LCN2; Osteoblast; Tissue engineering

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.146674