bims-engexo Biomed News
on Engineered exosomes
Issue of 2025–11–30
thirteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Engineered NK92 cell-derived exosomes inhibit ovarian cancer progression by degrading GPRC5A.
  2. Advances in Intranasal Delivery of Exosomes for Central Nervous System Disorders.
  3. CAP-CD56+CD271+ BMSCs exos-loaded PVA/SA sustained-release hydrogel attenuates chondrocyte senescence and ameliorates lumbar facet joint osteoarthritis.
  4. Lymph node delivery of immunogenic dendritic cell exosomes via extended-tip microneedles for cancer prevention.
  5. Engineered Dendritic Cell-Derived Vesicles for T-Cell-Targeted Magnesium Delivery and Metabolic Reprogramming.
  6. [Role and Mechanism of Hyaluronic Acid-modified Milk Exosomes 
in Reversing Pemetrexed Resistance in Lung Adenocarcinoma Cells].
  7. Breaking barriers: Engineering extracellular vesicles for enhanced endosomal escape and therapeutic delivery.
  8. Hacking Extracellular Vesicles: Using Vesicle-Related Tags to Engineer Mesenchymal Stromal Cell-Derived Extracellular Vesicles.
  9. Exosomes derived from miR-26a-5p-modified adipose mesenchymal stem cells improve wound healing by targeting MAP2K4.
  10. Extracellular vesicle-based protein and RNA delivery.
  11. Double-Responsive Macrophage-Derived Exosomes Alleviate Acute Lung Injury.
  12. Biocontrol of Root-Knot Nematodes via siRNA-Loaded Extracellular Vesicles From a Nematophagous Fungus Arthrobotrys oligospora.
  13. Engineered plant extracellular vesicles: Emerging nanoplatforms for combinational cancer immunotherapy.
  1. Front Immunol. 2025 ;16 1613178
    Engineered NK92 cell-derived exosomes inhibit ovarian cancer progression by degrading GPRC5A.
    Chaohua Si, Yihan Wang, Yuanyuan Li, Yuqi Chen, Yuxuan Fan, Yunwen Wang, Yanan Tian, Jianen Gao, Xu Ma.
       Background: Natural killer (NK) 92 (NK92) cells are critical immune-effectors with established roles in treating metastatic and hematological malignancies. Owing to the substantial adverse effects, including cytokine release syndrome, associated with NK92 cell therapy, research interest has pivoted toward the safer and potentially more efficient exosome-based approaches. However, the composition, properties, and functions of NK92 cell-derived exosomes remain largely unknown.
    Methods: In this study, NK92 cell-derived exosomes were isolated via ultracentrifugation. Small RNA sequencing and proteomic sequencing were performed on both the cells and their exosomes. To enhance exosome targeting to tumor cells, the tLyP-1 targeting peptide was displayed on NK92 cell surfaces through genetic engineering. The mechanism underlying tumor therapy mediated by NK92 cell-derived exosomes was investigated through in vitro and in vivo experiments. Additionally, we designed a cholesterol-modified ABCB1 siRNA that adsorbs onto exosome surfaces and enters recipient cells to silence target genes.
    Results: First, small RNA sequencing and proteomic analysis of NK92 cells and NK92 cell-derived exosomes revealed that the exosomes retained the anti-tumor activity of parental NK cells, inhibiting tumor progression by modulating apoptosis, proliferation, and metastasis. Second, tLyP-1-modified exosomes exhibited enhanced tumor-targeting specificity and exerted anti-tumor effects via the miR-31-5p-GPRC5A axis. Furthermore, NK92 cell-derived exosomes effectively delivered ABCB1 siRNA into recipient cells, mediating efficient gene silencing to sensitize chemoresistant ovarian cancer cells to therapeutic agents.
    Conclusion: Overall, this study provides a novel strategy to treat ovarian cancer through the preparation of genetically modified NK92 cell-derived exosomes loaded with RNA interference.
    Keywords:  exosome; miRNA; natural killer 92 cells; siRNA; tLyP-1
    DOI:  https://doi.org/10.3389/fimmu.2025.1613178
  2. Mol Neurobiol. 2025 Nov 27. 63(1): 193
    Advances in Intranasal Delivery of Exosomes for Central Nervous System Disorders.
    Babak Arjmand, Ali Reza Mojavezi, Amirhossein Kamroo, Rosa Kalami Yazdi, Mostafa Rezaei-Tavirani, Mohamad-Sadegh Vahedi.
      Central nervous system disorders are major global health challenges that contribute to significant morbidity and mortality. Traditional therapeutic strategies often face substantial limitations, primarily due to the blood-brain barrier, which restricts the delivery of pharmacological agents to the brain and consequently affects treatment effectiveness. In recent years, in order to enhance the efficacy of the central nervous system treatments, exosome-based approaches have gained interest. Exosomes, small extracellular vesicles (30-150 nm) secreted by cells, present a feasible therapeutic strategy due to their ability to cross the blood-brain barrier and transport bioactive molecules. Reflecting the traits of their parent cells (e.g., glioma stem cells and glioblastoma multiforme), exosomes can be isolated from body fluids, which enhances their clinical applicability. Additionally, intranasal delivery provides a non-invasive method to administer exosomes, using the olfactory and trigeminal nerve pathways to bypass the blood-brain barrier and directly target the brain. This method shows great promise in enhancing therapeutic efficacy for CNS disorders. However, challenges such as rapid mucociliary clearance, enzymatic degradation, and limited bioavailability reduce efficacy. Advances in exosome engineering, nanocarrier systems, and novel delivery devices are under investigation to mitigate these constraints. However, clinical translation requires further research to guarantee safety, consistency, and scalability. In this context, intranasal exosome delivery holds considerable promise as a non-invasive strategy for central nervous system disorder treatment, contingent on overcoming the current biological and technical barriers.
    Keywords:  Blood-brain barrier; Central nervous system disorders; Exosomes; Intranasal delivery; Nanocarrier engineering; Therapeutic loading
    DOI:  https://doi.org/10.1007/s12035-025-05563-4
  3. Bioact Mater. 2026 Mar;57 73-92
    CAP-CD56+CD271+ BMSCs exos-loaded PVA/SA sustained-release hydrogel attenuates chondrocyte senescence and ameliorates lumbar facet joint osteoarthritis.
    Yong Xie, Quanbo Liu, Jinghua Tan, Yingjie Lu, Yunlong Li, Hongyi Ye, Zhun Xu, Ming Wang, Cheng Wang, Xuelin Li, Jingbo Xue, Yiguo Yan.
       Objective: This study aimed to develop a novel, targeted therapy for lumbar facet joint osteoarthritis (LFJ OA) by identifying a potent bone mesenchymal stem cell (BMSC) subpopulation for cartilage regeneration, engineering its exosomes (Exos) for specific delivery, and incorporating them into a sustained-release hydrogel system. The study also aimed to elucidate the underlying molecular mechanism.
    Methods: A CD56+CD271+ BMSCs subpopulation with potent cartilage regeneration potential within the human bone marrow was identified through single-cell RNA sequencing and then isolated. Exos were subsequently extracted from this specific subpopulation and engineered with a chondrocyte-specific antigen peptide (CAP) to generate CAP-CD56+CD271+ BMSCs Exos. A polyvinyl alcohol (PVA)/sodium alginate (SA) composite hydrogel was developed to serve as a sustained-release carrier for these targeted exosomes. Finally, the efficacy of the composite system was rigorously evaluated both in vitro and in vivo, and mechanistic insights were pursued through sequencing and molecular experiments.
    Results: Compared with conventional BMSCs, the CD56+CD271+ BMSCs subpopulation and its derived exosomes demonstrated significantly enhanced pro-chondrogenic and anti-senescence capabilities compared to conventional BMSCs. CAP modification substantially improved in vivo targeting efficiency to chondrocytes, whereas the PVA/SA hydrogel enabled sustained exosome release, prolonging retention at injury sites. Implantation of the integrated CAP-Exos-PVA/SA system markedly improved osteoarthritis cartilage structure, increased matrix deposition, and suppressed the expression of matrix metalloproteinase-13 (MMP-13) and senescence markers (p16/p21/p53). Mechanistic studies revealed that the Exo-mediated delivery of miR-210-3p inhibited hypoxia-inducible factor-3α (HIF-3α) expression in chondrocytes. These therapeutic effects were abolished upon miR-210-3p blockade or HIF-3α overexpression.
    Conclusion: The CAP-CD56+CD271+ BMSCs Exos-PVA/SA hydrogel sustained-release system presents a promising and effective therapeutic approach for LFJ OA.
    Keywords:  Bone marrow mesenchymal stem cell; Engineered exosomes; Lumbar facet joint osteoarthritis; Senescence
    DOI:  https://doi.org/10.1016/j.bioactmat.2025.10.027
  4. J Control Release. 2025 Nov 25. pii: S0168-3659(25)01078-8. [Epub ahead of print] 114464
    Lymph node delivery of immunogenic dendritic cell exosomes via extended-tip microneedles for cancer prevention.
    Shijie Zhao, Yubing Guo, Yue Yin.
      Cancer prevention remains a significant challenge due to the ubiquitous presence of potentially malignant cells in the body. This study presents a novel cancer vaccine platform aimed at training the immune system to prevent the development of solid tumors. We engineered a nanostimulator (nano-IS3) comprising survivin-encoding plasmid DNA, polyethylenimine, and interferon-β-expressing nanoprotoplasts to activate dendritic cells (DCs), producing immunogenic exosomes enriched with survivin-derived antigens and costimulatory molecules (IdE@S). These IdE@S were loaded into long-tipped dissolvable microneedle patches (HdMN-IdE@S) designed to penetrate the dermis for enhanced delivery to draining lymph nodes. In vitro studies demonstrated enhanced T cell activation by IdE@S compared to conventional exosomes. In vivo, the HdMN-IdE@S vaccine induced robust CD8+ T cell responses, potentially enabling continuous immune surveillance against emerging cancer cells. Importantly, this prevention strategy showed no systemic toxicity or organ damage. This approach offers a potent, safe, and patient-friendly method for cancer prevention, potentially advancing the clinical translation of tumor-associated antigen-based immunotherapies for maintaining long-term cancer-free status.
    Keywords:  CD8(+) T cell; Cancer prevention; Dendritic cell-derived exosomes; Long-tipped dissolvable microneedles; Lymph node-targeted delivery; Survivin
    DOI:  https://doi.org/10.1016/j.jconrel.2025.114464
  5. ACS Nano. 2025 Nov 25.
    Engineered Dendritic Cell-Derived Vesicles for T-Cell-Targeted Magnesium Delivery and Metabolic Reprogramming.
    Xiaoyu Yu, Shuqi Chen, Rong Sun, Chenlu Yao, Bingbing Wu, Heng Wang, Chenhui Weng, Dongdong Sun, Chao Wang, Fang Xu.
      The tumor microenvironment (TME) fosters immunosuppression and T-cell exhaustion, which limit the efficacy of immunotherapy. Magnesium ions (Mg2+) have recently been identified as potent immunomodulators that enhance cytotoxic T lymphocyte (CD8+ T) activity. However, conventional carriers for Mg2+ delivery suffer from poor biocompatibility and inefficient targeting, restricting therapeutic outcomes. In this study, we developed an engineered extracellular vesicle (EV)-based system for targeted Mg2+ delivery. Dendritic cells were genetically modified to overexpress magnesium-specific channel protein MgtE (SLC41A1), enabling efficient Mg2+ encapsulation into dendritic cell-derived EVs (E-DEVs). The resulting Mg2+-loaded vesicles (E-DEVs@Mg2+) displayed strong tropism toward tumor-draining lymph nodes (TDLNs) and effectively modulated T-cell metabolism. Mechanistic studies revealed that E-DEVs@Mg2+ enhanced glycolysis and oxidative phosphorylation, restoring the metabolic fitness of exhausted CD8+ T cells. When combined with immune checkpoint blockade therapy, this strategy achieved a synergistic tumor suppression. Our findings highlight engineered DEVs as a biocompatible and effective Mg2+ delivery platform, providing a promising approach for metabolic reprogramming and improved cancer immunotherapy.
    Keywords:  Immunoengineering; dendritic cells; extracellular vesicles; immunotherapy technology; magnesium ions
    DOI:  https://doi.org/10.1021/acsnano.5c14528
  6. Zhongguo Fei Ai Za Zhi. 2025 Sep 20. 28(9): 658-666
    [Role and Mechanism of Hyaluronic Acid-modified Milk Exosomes 
in Reversing Pemetrexed Resistance in Lung Adenocarcinoma Cells].
    Lan Wu, Jie Lei, Hui Li.
       BACKGROUND: Lung cancer currently ranks first globally in both incidence and mortality. Pemetrexed (PMX) serves as a first-line treatment for lung adenocarcinoma (LUAD), but the patients often develop drug resistance during therapy. Milk exosome (mEXO) have the advantages of low immunogenicity, high tissue affinity, and low cost, and mEXO itself has anti-tumor effects. Hyaluronan (HA) naturally bind to CD44, a receptor which is highly expressed in LUAD tissues. This study aims to construct hyaluronan-modified milk exosome (HA-mEXO) and preliminarily investigate their molecular mechanisms for reversing PMX resistance through cellular experiments.
    METHODS: Exosomes were extracted from milk using high-speed centrifugation, and HA-mEXO was constructed. PMX-resistant A549 and PC-9 cell lines were treated with mEXO and HA-mEXO, respectively. CCK-8 assays, colony formation assays, Transwell assays, and flow cytometry were performed to evaluate proliferation, colony formation, migration, invasion, and apoptosis phenotypes in the treated resistant cell lines. Finally, transcriptomic sequencing, analysis, and cellular functional recovery experiments were conducted to investigate the mechanism by which HA-mEXO reverses PMX resistance in LUAD cells.
    RESULTS: The expression of CD44 in A549 and PC-9 LUAD drug-resistant cell lines was significantly higher than that in parental cells, and the uptake rate of HA-mEXO by drug-resistant cell lines was significantly higher than that of mEXO. Compared to the mEXO group, HA-mEXO-treated A549 and PC-9 resistant cells exhibited significantly reduced half maximal inhibitory concentration (IC50) values for PMX, markedly diminished clonogenic, migratory, and invasive capabilities, and a significantly increased proportion of apoptotic cells. Western blot analysis revealed that, compared to parental cells, A549 and PC-9 drug-resistant cells exhibited downregulated ZNF516 expression and upregulated ABCC5 expression. Immunofluorescence analysis revealed that HA-mEXO treatment downregulated ABCC5 expression in A549 and PC-9 drug-resistant cells compared to the PBS group, whereas co-treatment with HA-mEXO and ZNF516 knockdown showed no significant change in ABCC5 expression.
    CONCLUSIONS: HA-mEXO carrying ZNF516 suppress ABCC5 expression, thereby enhancing the sensitivity of A549 and PC-9 LAUD drug-resistant cells to PMX.
    Keywords:  Drug resistance; Exosomes; Hyaluronic acid; Lung neoplasms; Pemetrexed
    DOI:  https://doi.org/10.3779/j.issn.1009-3419.2025.102.35
  7. J Control Release. 2025 Nov 22. pii: S0168-3659(25)01076-4. [Epub ahead of print]389 114462
    Breaking barriers: Engineering extracellular vesicles for enhanced endosomal escape and therapeutic delivery.
    Jihong Kim, Yeong Ha Hwang, Gi-Hoon Nam, In-San Kim.
      Extracellular vesicles (EVs) have emerged as promising natural nanocarriers with superior biocompatibility, immune tolerance, and tissue tropism compared to synthetic nanoparticles. However, despite their efficient cellular uptake, the clinical translation of EV-based therapeutics is fundamentally constrained by inefficient endosomal escape, which remains the principal bottleneck to achieving functional cytosolic delivery. To address this challenge, a variety of engineering strategies have been developed, including post-isolation surface decoration with peptides and polymers, genetic incorporation of fusogenic proteins and channel-forming modules, and biophysical remodeling of membrane lipid composition. These modifications aim to enhance intracellular delivery by improving membrane fusion and facilitating endosomal membrane destabilization. Concurrently, the development of advanced quantitative assays has enabled more accurate evaluation of endosomal escape efficiency. This review summarizes recent advances in engineering approaches and analytical methodologies and discusses future perspectives for overcoming biological and manufacturing hurdles to realize the clinical potential of EV-based therapeutics.
    Keywords:  Endosomal escape; Endosomal escape evaluation; Engineered extracellular vesicles; Genetic engineering; Membrane remodeling; Surface decoration
    DOI:  https://doi.org/10.1016/j.jconrel.2025.114462
  8. Pharmaceutics. 2025 Nov 06. pii: 1435. [Epub ahead of print]17(11):
    Hacking Extracellular Vesicles: Using Vesicle-Related Tags to Engineer Mesenchymal Stromal Cell-Derived Extracellular Vesicles.
    Gabriele Scattini, Giulia Pianigiani, Stefano Capomaccio, Maria Rachele Ceccarini, Samanta Mecocci, Laura Musa, Luca Avellini, Olimpia Barbato, Antonello Bufalari, Patrizia Casagrande Proietti, Rodolfo Gialletti, Alessia Sulla, Tommaso Beccari, Luisa Pascucci.
      Background/Objectives: Extracellular Vesicles (EVs) have shown great promise as diagnostic and therapeutic tools, as well as pharmacological nanocarriers. Various strategies are being explored to develop EVs for monitoring, imaging, loading with pharmacological agents, and surface decoration with tissue-specific ligands. EVs derived from Mesenchymal Stromal Cells (MSC-EVs) are of particular interest both as therapeutics per se and as natural nanocarriers for the targeted delivery of biotherapeutics. Methods: In this study, we investigated the ability of different tags to deliver a reporter protein into canine MSC-EVs with the aim of identifying the most effective endogenous loading mechanism. To this aim, canine MSCs were engineered to express the Green Fluorescent Protein (GFP) fused to CD63, Syntenin-1, TSG101, and the palmitoylation signal of Lck, which were expected to promote GFP incorporation into EVs. Overexpression of tagged GFP in canine MSCs was confirmed by Western blotting and examined by confocal microscopy and transmission electron microscopy to map intracellular localization. Results: All tags were able to deliver GFP into EVs. Syntenin-1 showed relatively high loading efficiency and secretion index but exhibited a diffuse localization pattern in the transfected cells. The palmitoylation signal showed low loading efficiency and localization specificity. TSG101 displayed a morphological pattern consistent with specific localization in endosomal structures, but its low expression level prevented further evaluations. Finally, CD63 showed the highest expression efficiency, as GFP-CD63 levels were approximately 5-fold higher than untagged GFP. Conclusions: In conclusion, CD63 emerged as the most suitable tag for canine MSC-EV engineering. Indeed, even if the secretion index favours Syntenin-1, CD63's higher abundance in the lysate suggests its substantial post-secretion uptake. Further studies aimed at elucidating CD63's specific contribution and identifying the domains involved in vesicle trafficking could provide valuable insights into EV bioengineering.
    Keywords:  CD63; EVs engineering; GFP; Mesenchymal Stromal Cells; Palmitoylation; Syntenin; TSG101; extracellular vesicles; transfection
    DOI:  https://doi.org/10.3390/pharmaceutics17111435
  9. Front Bioeng Biotechnol. 2025 ;13 1662095
    Exosomes derived from miR-26a-5p-modified adipose mesenchymal stem cells improve wound healing by targeting MAP2K4.
    Kana Chen, Wei Ye, Longjun Chi, Shujie Xie.
       Introduction: Abnormal wound healing impairs bodily functions and burdens healthcare systems. Adipose mesenchymal stem cells (AMSCs)-derived exosomes promote wound healing, with exosomal microRNAs (miRNAs) playing pivotal roles. This study investigated the roles and mechanisms of miR-26a-5p (delivered by AMSCs-derived exosomes) in wound healing.
    Methods: The GSE55661 dataset was analyzed to screen a crucial miRNA (miR-26a-5p) and its target gene (MAP2K4), and their interaction was further validated by dual-luciferase reporter gene assay. Exosomes were isolated from miR-26a-5p-overexpressing AMSCs, and a mouse skin defect model was used to evaluate their effects on wound healing.
    Results: Bioinformatics identified 13 differentially expressed miRNAs, and a miRNA-mRNA regulatory network composed of 12 DEmiRNAs and 143 regulated target genes was built. In this network, miR-26a served as the hub node, and the target genes were enriched in the MAPK cascade, as well as cAMP, relaxin, Hippo, Apelin, Wnt, and cGMP-PKG signaling pathways. Thereafter, MAP2K4 was identified as the target of miR-26a-5p, and exosomes were successfully isolated from AMSCs overexpressing miR-26a-5p. Exosomes from miR-26a-5p overexpressed AMSCs (like miR-26a-5p agomir) could facilitate wound healing, and down-regulated MAP2K4, Il6, Il1β, and Tnf-α, whereas up-regulated Col1a1, Cd31, Col2a1, α-Sma, and Col3a1.
    Discussion: AMSCs-derived exosomes delivering miR-26a-5p may expedite wound healing by targeting MAP2K4, inhibiting inflammation, and enhancing angiogenesis and ECM synthesis.
    Keywords:  AMSCs-derived exosomes; MAP2K4; angiogenesis; miR-26a-5p; wound healing
    DOI:  https://doi.org/10.3389/fbioe.2025.1662095
  10. Int J Pharm. 2025 Dec 25. pii: S0378-5173(25)01137-8. [Epub ahead of print]686 126300
    Extracellular vesicle-based protein and RNA delivery.
    Tiantian Li, Haonan Xing, Yuanyu Huang, Mei Lu.
      The field of protein and RNA therapies has revolutionized the treatment of numerous diseases with the regulatory approval of diverse products during the past few decades. However, the application of protein and RNA therapies has consistently faced significant challenges that substantially impact their safety, stability, bioavailability, and therapeutic efficacy. Consequently, the development of efficient delivery platforms is paramount to amplifying their therapeutic effect and broadening their clinical application. To date, a wide range of nanocarriers have been developed and made great progresses in the field. Extracellular vesicles (EVs) have emerged as a terrific arsenal for designing protein and RNA delivery platforms, due to several beneficial properties. In addition to low immunogenicity and excellent safety, EVs are naturally occurring protein and RNA delivery vehicles with intrinsic ability to protect cargoes from degradation and good membrane permeability. This review delves into the latest advances in EV-based protein and RNA delivery systems with focus on various endogenous and exogenous engineering approaches. Furthermore, this document provides a discussion on the application of EV-based protein and RNA therapies in diseases, as well as the advancements in clinical research related to these therapies.
    Keywords:  Delivery systems; Extracellular vesicles; Proteins; RNAs; Therapeutics; Vaccines
    DOI:  https://doi.org/10.1016/j.ijpharm.2025.126300
  11. Biomater Res. 2025 ;29 0277
    Double-Responsive Macrophage-Derived Exosomes Alleviate Acute Lung Injury.
    Chunhua Ma, Zhaocong Yang, Jing Wang, Xuemei Li, Tao Li, Liangming Liu.
      Acute lung injury (ALI) is one of the complications of sepsis, and macrophages play an important role in ALI. The aim of this research was to investigate the effects of epidermal growth factor receptor (EGFR) monoclonal antibody-modified chemokine (C-X-C motif) ligand 8 (CXCL8) overexpression of macrophage (CXCL8@M)-derived exosomes miR-126a-3p (EGFR@CXCL8@exo-miR-126a-3p) on sepsis ALI. CXCL8@M was obtained via macrophage infection of CXCL8 plasmid, and CXCL8-M-exo was obtained via an exosome extraction kit. In addition, hsa-miR-126-3p agomir [a specially chemically modified microRNA (miRNA) mimic, named miR-126-3p] was loaded in CXCL8@M-exo to form CXCR8@exo-miR-126a-3p via electroporation technology. Further, EGFR@CXCR8@exo-miR-126a-3p was obtained via EGFR monoclonal antibody-modified CXCR8@exo-miR-126a-3p. Lipopolysaccharide (LPS)-induced ALI models were used to evaluate the role and mechanism of EGFR@CXCR8@exo-miR-126a-3p on ALI. Single-cell sequencing and miRNA chip results showed that miR-126a-3p was mainly expressed in pulmonary macrophages and markedly decreased, while single-cell sequencing and immunofluorescence results showed that EGFR was expressed and significantly elevated in macrophages in ALI mice. miR-126a-3p and EGFR siRNA significantly inhibited polarization of M1 macrophage. The imaging results of small animals showed that EGFR@CXCL8-exo-miR-126a-3p has obvious macrophage targeting. The results showed that EGFR@CXCR8@exo-miR-126a-3p significantly inhibited M1 macrophage and increased Treg cells to exert anti-inflammatory effects. The mechanism of EGFR@CXCR8@exo-miR-126a-3p on ALI is mainly via inhibition of PIK3R2/NLRP3 signaling pathway and ferroptosis. This study provided a new treatment method for ALI.
    DOI:  https://doi.org/10.34133/bmr.0277
  12. Microb Biotechnol. 2025 Nov;18(11): e70274
    Biocontrol of Root-Knot Nematodes via siRNA-Loaded Extracellular Vesicles From a Nematophagous Fungus Arthrobotrys oligospora.
    Xinyi Huang, Wenliang Zhou, Xiaoying Liu, Ke-Qin Zhang, Juan Li.
      Root-knot nematodes (Meloidogyne spp.) represent a major threat to global crop production, and current chemical nematicides pose serious environmental and health risks. RNA interference (RNAi) offers a promising gene-specific strategy for nematode control. However, the efficient and sustainable delivery of RNA molecules into nematodes remains a significant challenge. In this study, we developed an innovative RNA delivery platform using extracellular vesicles (EVs) derived from the nematode-trapping fungus Arthrobotrys oligospora. EVs were either exogenously loaded with synthetic siRNAs targeting the Mi-flp-18 gene of M. incognita or harvested from engineered fungal strains expressing short hairpin RNAs (shRNAs) or double-stranded RNAs (dsRNAs) against multiple nematode neuropeptide genes (flp and nlp families). The engineered EVs efficiently delivered RNA cargos into nematodes, leading to significant downregulation of target gene expression. Functional assays and greenhouse experiments revealed the biocontrol potential of the engineered fungal strains, with reductions in nematode motility, root invasion and infectivity. This is the first demonstration in a nematophagous fungus that EVs can serve as effective RNA delivery vehicles for the control of root-knot nematodes. The use of engineered A. oligospora strains provides a scalable, eco-friendly alternative to synthetic delivery systems and transgenic crops. Our findings establish fungal EVs as a powerful tool in cross-kingdom RNAi applications and open new avenues for sustainable pest management in agriculture.
    Keywords:   Arthrobotrys oligospora ; Meloidogyne incognita ; RNA interference; biocontrol; cross‐kingdom communication; extracellular vesicles; neuropeptides
    DOI:  https://doi.org/10.1111/1751-7915.70274
  13. Acta Pharm Sin B. 2025 Nov;15(11): 5663-5701
    Engineered plant extracellular vesicles: Emerging nanoplatforms for combinational cancer immunotherapy.
    Fucai Chen, Rongrong Bao, Wanyi Yang, Yijing Lu, Jiaxin Guo, Wenjing Chen, Jiale Li, Kuanhan Feng, Wen Zhang, Liuqing Di, Liang Feng, Ruoning Wang.
      Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.
    Keywords:  Cancer immunotherapy; Clinical transformation; Combinational cancer immunotherapy; Drug loading techniques; Engineering strategies; Novel nanoplatforms; Pharmacokinetics; Plant-derived extracellular vesicles
    DOI:  https://doi.org/10.1016/j.apsb.2025.08.020
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