bims-engexo Biomed News
on Engineered exosomes
Issue of 2026–03–15
fifteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Exosome Engineering for Blocking Gut Dysbiosis and Inducing Cell Death Mechanisms in Glioblastoma Multiforme.
  2. ABA-Induced Cargo Proteins Loading in Extracellular Vesicles for Gene Editing.
  3. A novel microneedle-based delivery of NRF2-overexpressing exosomes for scleroderma therapy.
  4. Extracellular vesicle engineering using a small scaffold protein.
  5. An Engineered Extracellular Vesicle With Enhanced Tumor and Lymph Nodes Targeting as siRNA Delivery System for Robust Tumor Immunotherapy.
  6. Comparison of Exosome- and Hybrosome-Based Therapies in Regenerative Medicine and Cell Aging: A Narrative Review.
  7. Engineered CAR-T-Derived Exosomes Co-Delivering miR-145 and Cytotoxic Proteins for Targeted Solid Tumour Therapy.
  8. From Biointelligence to Biointerference: Exosomes as Bioengineered Cellular Communicators Transforming Regenerative Medicine.
  9. Development of Mesenchymal Stem Cell Membrane-Enveloped Nanovesicles for Enhanced Gene Delivery.
  10. Protocatechualdehyde-functionalized BMSC-derived exosomes orchestrate calcium signaling in the immunoinflammatory microenvironment to promote periodontal regeneration.
  11. lncRNA-Driven Multi-omics Reconstitution Engineers EVs for Macrophage-Targeted and Anti-Inflammatory Therapy in MASLD.
  12. Nebulized delivery of multi-modular stem cell-derived exosomes for the treatment of pulmonary fibrosis.
  13. Engineering Optimized EV-Mimetic Carriers for Efficient Tumor-Targeted Delivery of Functional RNA Nanoparticles.
  14. Engineering MSC-exosomes for diabetic bone regeneration: from mechanism to delivery.
  15. Microneedle-based delivery of cell membrane vesicles as IL-17RA decoys for Psoriasis treatment.
  1. Cells. 2026 Feb 27. pii: 422. [Epub ahead of print]15(5):
    Exosome Engineering for Blocking Gut Dysbiosis and Inducing Cell Death Mechanisms in Glioblastoma Multiforme.
    Ahalya Muraleedharan, Karthik Rangavajhula, Swapan K Ray.
      Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. Emerging evidence endorses that gut dysbiosis contributes to GBM progression through the gut-brain axis (GBA), promoting inflammation and therapeutic resistance via abnormal short-chain fatty acid production and cytokine dysregulation. Exosomes, naturally occurring nanovesicles (30-150 nm), offer promising therapeutic potential due to their blood-brain barrier permeability, biocompatibility, and versatile cargo capacity. This review examines exosome engineering strategies for dual targeting: inhibiting alterations in gut microbiome and inducing regulated cell death mechanisms such as apoptosis and ferroptosis in GBM. We describe exosome engineering with detailed focus on cargo loading approaches (e.g., genetic modification, electroporation, and sonication), exosome surface functionalization with specific ligands (e.g., antibodies), and exosome biogenesis pathway manipulation. Engineered exosomes can deliver anti-inflammatory agents and gut microbiome modulators to restore GBA homeostasis while simultaneously transporting tumor-suppressive non-coding RNAs (e.g., miRNAs, siRNAs) and therapeutic agents to induce apoptosis by overcoming temozolomide resistance, and trigger ferroptosis-inducing components in GBM stem cells. Preclinical studies make obvious that this dual-targeting approach ought to enhance therapeutic efficacy by creating systemic immunity and eliminating tumor cells. However, clinical translation brings forth challenges, such as manufacturing, targeting specificity, and standardized quality control, and warrants further study.
    Keywords:  apoptosis; exosome biogenesis and cargo loading; exosome engineering; ferroptosis; glioblastoma multiforme; gut dysbiosis
    DOI:  https://doi.org/10.3390/cells15050422
  2. Cells. 2026 Feb 26. pii: 405. [Epub ahead of print]15(5):
    ABA-Induced Cargo Proteins Loading in Extracellular Vesicles for Gene Editing.
    Sai Wei, Jian Li, Huacan Tuo, Wei Wang, Guo Li, Luan Wen.
      Extracellular vesicles, which carry bioactive cargos such as proteins, RNAs, and lipids, represent promising drug delivery vehicles owing to their biocompatibility, low immunogenicity, and inherent tissue-targeting capabilities. To address the current limitations in controlled cargo loading, we developed an abscisic acid (ABA)-inducible proximity system that directs proteins into exosomes during biogenesis. We engineered exosomal scaffolds by fusing the ABA receptor PYL1 to EV-enriched proteins-including BASP1, CD9, PTGFRN, and a truncated form PTGFRNΔ687-thereby creating docking sites within the exosomal lumen, while the target cargo (e.g., EGFP, firefly luciferase, or Cas9) was tagged with the ABI1 phosphatase domain. We demonstrate that ABA administration in producer cells induces PYL1-ABI1 complex formation, which recruits ABI1-fused cargo for selective encapsulation into EVs. Among the scaffolds tested, BASP1-PYL1 proved the most effective, enabling robust, ABA-dependent enrichment of cargo proteins. Purified EVs maintained canonical morphology, size, and marker expression (CD63, syntenin-1, CD9), confirming preserved biogenesis. Critically, these loaded exosomes efficiently delivered functional cargo to recipient cells, enabling Cas9/sgRNA-mediated genome editing. Together, our findings establish an ABA-triggered molecular switch for controllable EV protein loading, providing a versatile platform for next-generation therapeutic delivery.
    Keywords:  Cas9; abscisic acid (ABA); chemically induced proximity; extracellular vesicles (EVs); protein loading
    DOI:  https://doi.org/10.3390/cells15050405
  3. Int J Biol Macromol. 2025 Dec;pii: S0141-8130(25)09007-5. [Epub ahead of print]334(Pt 1): 148450
    A novel microneedle-based delivery of NRF2-overexpressing exosomes for scleroderma therapy.
    Zi-Ming Li, Jie-Yu Xiang, Song-Lu Tseng, Tian-Hao Li, Li-Quan Wang, Lin Kang, Jiu-Zuo Huang, Nan-Ze Yu, Xiao Long.
      Scleroderma is a chronic autoimmune connective tissue disease characterized by progressive skin fibrosis, vascular dysfunction, and immune dysregulation. Current therapies remain largely ineffective in reversing established fibrosis and are limited by systemic side effects. In this study, we developed a novel therapeutic strategy combining microneedle (MN)-mediated transdermal delivery with NRF2-overexpressing exosomes (NRF2-OE Exos) to locally enhance antioxidant, anti-fibrotic, anti-inflammatory, and pro-angiogenic effects in scleroderma. Exosomes were isolated from NRF2-OE adipose-derived stem cells (ADSCs) and incorporated into GelMA/PEGDA-based dissolvable MNs. These MNs demonstrated excellent mechanical strength, minimal invasiveness, sustained exosome release, and efficient cellular uptake in vitro. Functional assays showed that NRF2-OE Exos-loaded MNs significantly enhanced endothelial tube formation, preserved fibroblast mitochondrial integrity, and promoted macrophage polarization toward a reparative phenotype. In a bleomycin-induced murine scleroderma model, MN treatment reduced dermal thickening, collagen deposition, and α-SMA expression while promoting vascular regeneration and immunomodulation. Mechanistically, transcriptomic analysis revealed that NRF2-OE Exos suppressed pro-fibrotic Wnt and Hippo signaling pathways and activated calcium and cAMP signaling pathways. Moreover, NRF2-OE Exos alleviated mitochondrial dysfunction and ferroptotic injury by upregulating antioxidant and lipid peroxidation defense genes. Collectively, this study demonstrates that MN-mediated delivery of engineered exosomes offers a promising, localized, and multifaceted therapeutic approach for scleroderma, with strong translational potential.
    Keywords:  ADSCs derived exosomes; Microneedles; Scleroderma
    DOI:  https://doi.org/10.1016/j.ijbiomac.2025.148450
  4. Nat Commun. 2026 Mar 10.
    Extracellular vesicle engineering using a small scaffold protein.
    Wenjing Yan, Shizhi Wang, Haibin Hao, Hong Lin, Chen Wang, Shuqian Xie, Xing Zhang, Yiran Lu, Xin Ding, Xue Chen, Haohan Liu, Guiyuan Zhang, Dong Wei, ChangYan Ma, Cheng Tang, Xiuting Li, Bingjia Yu, Jing Hu, Zhongze Gu, Evan Yi-Wen Yu, Weiqin Li, Jiang Xia, Hao Zhang.
      Extracellular vesicles (EVs) are promising drug-delivery vehicles owing to their biocompatibility and low immunogenicity. Genetic engineering of a membrane-bound EV-sorting scaffold protein empowers EVs by installing targeting moieties on the surface and enriching therapeutic cargo in the lumen. However, the choice of scaffold proteins with simple structures and short sequences is limited. Here, we conduct mass spectrometry-based proteomic studies and identify ENPP1 as a superior scaffold protein. Furthermore, we show that a truncated 144-amino acid variant, EN144, efficiently loads diverse therapeutic cargoes and outperforms conventional scaffolds. By fusing EN144 to the IL-6 decoy receptor gp130, we create engineered decoy EVs that potently inhibit inflammatory IL-6 trans-signaling. In mouse models, these EVs reduce inflammation, improve survival in sepsis, and, when targeted to cartilage, alleviate tissue damage in osteoarthritis. Our work establishes EN144 as a minimal, high-performance scaffold for EV engineering and demonstrates its broad therapeutic potential for inflammatory diseases.
    DOI:  https://doi.org/10.1038/s41467-026-70451-x
  5. MedComm (2020). 2026 Mar;7(3): e70673
    An Engineered Extracellular Vesicle With Enhanced Tumor and Lymph Nodes Targeting as siRNA Delivery System for Robust Tumor Immunotherapy.
    Yusi Wang, Rui Zhang, Xuejing Zhou, Lin Tang, Die Hu, Yibing Zhang, Yuling Yang, Bailing Zhou, Li Yang.
      Tumor-derived extracellular vesicles (EVs) are a class of natural nanocarriers with phospholipid bilayers that show great promise as personalized cancer vaccine platforms due to their ability to carry tumor-specific antigens. However, their immunotherapeutic potential is hindered by limited tissue-specific targeting. In this study, we engineered tumor cell-derived EVs using an immunomodulatory peptide, DP7-C, to generate DP7-C engineered EVs (DP-EVs). These DP-EVs exhibited significantly enhanced accumulation in both lymph nodes and tumor tissues. Additionally, they demonstrated improved cellular uptake and facilitated more efficient endosomal escape. To further enhance the therapeutic efficacy, programmed cell death 1 ligand 1 targeting small interfering RNA (siPD-L1) was loaded into the DP-EVs, resulting in DP-EVs/siPD-L1. This formulation enabled concurrent suppression of PD-L1 expression in both dendritic cells (DCs) and tumor cells. In vivo experiments showed that DP-EVs/siPD-L1 significantly inhibited tumor growth and prolonged survival in tumor-bearing mice. The observed antitumor effect was attributed to the immune activation in the lymph nodes and the remodeling of the immunosuppressive tumor microenvironment (TME). Collectively, our findings demonstrate that DP-EVs/siPD-L1 functions as an effective therapeutic vaccine, which synergistically activates antitumor immunity and reverses immunosuppression through targeted PD-L1 blockade. This engineered EV platform represents a promising and translatable strategy for cancer immunotherapy.
    Keywords:  extracellular vesicles; immune response activation; siRNA delivery; tumor immunotherapy; tumor microenvironment reprogramming
    DOI:  https://doi.org/10.1002/mco2.70673
  6. Aesthet Surg J. 2026 Mar 09. 46(Supplement_1): S26-S31
    Comparison of Exosome- and Hybrosome-Based Therapies in Regenerative Medicine and Cell Aging: A Narrative Review.
    Steven R Cohen, Jordan Wesson, Serli Canikyan, Tunc Tiryaki, Yaren Kul, Ceren Duyan.
      Exosomes have emerged as promising agents in regenerative medicine because of their ability to mediate intercellular communication, modulate inflammation, and promote tissue repair. However, their clinical application remains limited by issues of stability, bioavailability, and therapeutic consistency. Hybrosomes, engineered hybrid vesicles that combine exosomal membranes with liposomal structures, have been developed to enhance delivery, protect bioactive cargo, and prolong regenerative activity. The authors of this review aim to discuss the therapeutic efficacy of exosomes and hybrosomes in the context of skin regeneration and aesthetic procedures and evaluate their respective advantages and limitations. They aim to explore how bioengineered delivery systems may overcome current barriers to clinical translation. Studies were included if they evaluated exosome- or hybrosome-based interventions in wound healing or skin aging through in vitro, in vivo, or clinical models. Data regarding cellular proliferation, migration, angiogenesis, and inflammatory modulation were extracted and synthesized. The improved stability and delivery of hybrosomes enables sustained regenerative effects. The integration of liposomal architecture in hybrosomes may improve vesicle stability, extend bioactivity, and optimize delivery, potentially offering sustained regenerative benefits. However, future studies should include long-term clinical evaluations and standardized production protocols to establish hybrosome therapies as reliable and scalable interventions in regenerative and aesthetic medicine. Level of Evidence: 3 (Therapeutic).
    DOI:  https://doi.org/10.1093/asj/sjaf119
  7. J Extracell Vesicles. 2026 Mar;15(3): e70245
    Engineered CAR-T-Derived Exosomes Co-Delivering miR-145 and Cytotoxic Proteins for Targeted Solid Tumour Therapy.
    Ruyue Yang, Haitao Wang, Guidan Wang, Gankun Yuan, Zhaoyi Wei, Junling An, Dong Hu, Wenjing Wen, Shegan Gao, Yuan Wan, Gaofeng Liang.
      Chimeric antigen receptor T cell (CAR-T) therapy has demonstrated remarkable efficacy in haematologic malignancies but remains constrained in solid tumours due to limited tumour penetration, immunosuppressive microenvironments and the risk of cytokine release syndrome (CRS). Here, we develop a bioactive, cell-free therapeutic platform by engineering exosomes derived from B7-H3-targeted CAR-T cells and loading them with miR-145 (Name this exosome as exo-CT-145). The exosomes retain CAR-specific surface markers and cytotoxic payloads (perforin and granzyme), MiR-145 is expressed at low levels in various tumours and can inhibit the occurrence and development of tumours through multiple pathways. Exo-CT-145 significantly inhibited proliferation, migration, and Epithelial Mesenchymal Transition (EMT) of oesophageal squamous cell carcinoma (ESCC) cells and induced apoptosis in vitro. In vivo, exo-CT-145 demonstrated tumour-targeted accumulation, caspase-3 activation, EMT reversal, angiogenesis suppression and remodeling the tumor microenviroment while no detectable CRS or systemic toxicity. This study proposes a synergistic nanotherapeutic paradigm integrating antigen-specific killing and gene regulatory modulation, offering a promising direction for solid tumour treatment with improved safety and efficacy.
    Keywords:  angiopoiesis; chimeric antigen receptor T cell; epithelial mesenchymal transition; exosomes; microRNA‐145; oesophageal squamous cell carcinoma
    DOI:  https://doi.org/10.1002/jev2.70245
  8. Aesthet Surg J. 2026 Mar 09. 46(Supplement_1): S32-S37
    From Biointelligence to Biointerference: Exosomes as Bioengineered Cellular Communicators Transforming Regenerative Medicine.
    Tunc Tiryaki, Steven R Cohen, Serli Canikyan, Yaren Kul, Ceren Duyan, Ahmet Umut Yuvacı.
      Exosomes are nanoscale extracellular vesicles that facilitate intercellular communication by transporting regulatory molecules, such as microRNAs, proteins, and lipids. Acting as "software updates" for cells, exosomes influence gene expression and cellular behavior without altering the genetic code. Their emerging roles in tissue repair, immune modulation, and age-related rejuvenation have positioned them as promising tools in regenerative and aesthetic medicine. The authors of this systematic review aim to explore the therapeutic potential of natural and bioengineered exosomes, focusing on their mechanisms of action and applications in regenerative therapies and aesthetic interventions. A structured literature search was conducted across PubMed, Scopus, and Web of Science, including English-language studies available online as of April 2025. Eligible studies consisted of original in vitro, in vivo, and clinical research examining exosome-based applications in tissue regeneration, wound healing, and anti-aging therapies. Studies were thematically grouped by exosome origin, engineering strategy, and therapeutic context. A narrative synthesis approach was employed because of methodological heterogeneity. Exosomes represent a novel class of therapeutic agents capable of modulating biological processes critical to repair and regeneration. In addition to mammalian-derived vesicles, plant-based and hybrid systems offer scalable, biocompatible platforms for targeted molecular delivery. The integration of exosome-based therapies with advances in cellular reprogramming and bioelectric signaling may further expand their clinical utility. However, broader clinical adoption will require continued research addressing safety, manufacturing scalability, regulatory challenges, and ethical considerations. Level of Evidence: 3 (Therapeutic).
    DOI:  https://doi.org/10.1093/asj/sjaf076
  9. J Vis Exp. 2026 Feb 17.
    Development of Mesenchymal Stem Cell Membrane-Enveloped Nanovesicles for Enhanced Gene Delivery.
    Yue Su, Zaiyong An, Daopin Wu, Di Mu, Yaxuan Liang.
      Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) hold great promise for therapeutic applications and regenerative medicine. EVs are nanoscale vesicles secreted by all known cell types, carrying diverse cargos including membrane-anchored proteins, soluble factors, multiple RNA species, and metabolites that regulate the physiology and behavior of recipient cells. While MSC-derived or engineered EVs can deliver therapeutic proteins and RNAs, EV-mediated DNA delivery remains challenging due to the lack of efficient mechanisms for sorting DNA sequences into vesicles. Previous work from our group and others demonstrated that adeno-associated virus (AAV)-containing EVs enable targeted nuclear delivery and sustained gene expression in vitro and in vivo. However, their production and isolation have been limited by low yield and time-intensive procedures. Here, we report the development of MSC membrane-enveloped nanovesicles generated by a size-defined extrusion method for efficient gene delivery. These vesicles, approximately 200 nm in diameter, mimic the properties of natural EVs while encapsulating recombinant AAV vectors carrying therapeutic gene sequences. Compared with conventional AAVs, the engineered MSC vesicles improved gene delivery efficiency and achieved significantly higher yields with reduced time and cost relative to naturally secreted EV-AAVs. In summary, we present a novel MSC-based membrane nanovesicle platform that combines the advantages of EV-mimicking structures with AAV-mediated gene transfer. This approach enhances delivery efficiency and production scalability, offering a promising strategy to advance gene therapy toward clinical translation.
    DOI:  https://doi.org/10.3791/70316
  10. J Nanobiotechnology. 2026 Mar 07.
    Protocatechualdehyde-functionalized BMSC-derived exosomes orchestrate calcium signaling in the immunoinflammatory microenvironment to promote periodontal regeneration.
    Le Fan, Tianyou Wang, Meirui Ma, Yiqiao Wang, Xiaodong Wang, Xuan Tang, Yuanyuan Ma, Zhipeng Gu, Zhichao Hao.
      The significant global burden of periodontitis has increased over the past few decades. However, the regeneration and reconstruction of periodontal tissue remain major challenges in clinical practice. Successful periodontal treatment relies on the regulation of calcium signaling. Bone mesenchymal stem cell-derived exosomes (BMSC Exo) hold great potential for promoting calcium influx to enhance osteogenic differentiation, modulate the inflammatory microenvironment, and promote angiogenesis, but their therapeutic efficiency is limited by inadequate stability. To overcome this problem, a mild and facile approach using protocatechualdehyde was employed to modify BMSC Exo (PA@BMSC Exo) through covalent and noncovalent polyphenolic interactions. The resulting PA@BMSC Exo system enhanced the stability against external stress and augmented its ability to induce intracellular calcium entry. Osteogenesis in human periodontal ligament stem cells (hPDLSCs) and integrated periodontal regeneration in periodontitis were observed following PA@BMSC Exo treatment. Furthermore, these multifunctional PA@BMSC Exo also promoted immunoinflammatory regulation and neovascularization. Bioinformatic analysis based on RNA sequencing (RNA-seq) predicted that the osteogenic differentiation of hPDLSCs was enhanced by calcium influx mediated through the voltage-gated calcium channel Cav3.3. Intracellular Ca2+ levels were further validated in hPDLSCs, as well as in RAW264.7 cells and human umbilical vein endothelial cells (HUVECs). Overall, a facile engineered PA@BMSC Exo system was successfully developed to reverse periodontal destruction by orchestrating calcium signaling and the entire periodontal microenvironment, potentially opening a new avenue for the clinical treatment of chronic periodontitis.
    Keywords:  BMSC-derived exosomes; Calcium influx; Engineered EVs; Periodontitis; Polyphenolic protocatechualdehyde
    DOI:  https://doi.org/10.1186/s12951-026-04250-3
  11. Free Radic Biol Med. 2026 Mar 07. pii: S0891-5849(26)00213-3. [Epub ahead of print]
    lncRNA-Driven Multi-omics Reconstitution Engineers EVs for Macrophage-Targeted and Anti-Inflammatory Therapy in MASLD.
    Lin Liu, Guoen Li, Zhuoyan He, Yulong Sun, Ziming Jiao, Jiali Zhong, Ganglin Wang, Kaizhe Wang, Wei Li.
      Extracellular vesicles (EVs) can encapsulate and deliver diverse bioactive cargos, enabling multimolecular parallel communication and network-level regulation, and are emerging as promising nanotherapeutics. However, existing engineering strategies predominantly focus on single-function enhancement, limiting coordinated improvements in multi-dimensional regulation. As a proof of concept, we propose a lncRNA-driven multi-omics (transcriptomic and proteomic) reconstitution EV engineering strategy that leverages synergistic functional enhancement to generate multifunctional EVs (MF-EVs) with hepatic macrophage targeting and anti-inflammatory activity for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Using HEK293T as a chassis cells, overexpression of the lncENAF reprogrammed cellular states and increased EV yield by 40%. Proteomic and miRNA sequencing analyses revealed that the resulting MF-EVs are enriched for key molecular networks involved in inflammatory regulation and lipid metabolic homeostasis. Evidence from in vitro and in vivo studies demonstrated that MF-EVs exhibit efficient, selective delivery to hepatic macrophages, exert potent anti-inflammatory effects, and reduce the release of pro-inflammatory mediators. Functionally, MF-EVs significantly ameliorated hepatic inflammation and histopathological injury in high-fat diet-induced MASLD mice. Departing from conventional single-point enhancement, our approach treats lncRNA as a systems-level input to achieve endogenous, multidimensional reconfiguration of producer cells and their EVs, establishing an engineering route and conceptual basis for EV therapies targeting complex network diseases.
    Keywords:  LncENAF; anti-inflammation; engineered extracellular vesicles; macrophage; metabolic dysfunction-associated steatotic liver disease
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.03.022
  12. Nanomedicine. 2026 Mar 06. pii: S1549-9634(26)00026-2. [Epub ahead of print] 102925
    Nebulized delivery of multi-modular stem cell-derived exosomes for the treatment of pulmonary fibrosis.
    Xiaoyu Gao, Chunbin Sun, Yang Yang, Luping Li, Shuang Sha, Shanglin Cai, Liang Li, Zhongci Hang, Lei Wang, Cencan Xing, Hongwu Du.
      Pulmonary fibrosis (PF) is a terminal pathological manifestation of a group of lung diseases characterized by fibroblast proliferation, excessive extracellular matrix deposition, inflammatory damage, and structural destruction of lung tissue. The lung damage caused by PF is typically irreversible. Current medications and therapies can slow disease progression but fail to fully repair the damaged lung tissue. In this study, we developed a composite nanoparticle system from PNP@Exo using Poly(lactic-co-glycolic) acid (PLGA) as a carrier, which is capable of co-delivering the anti-fibrotic drug nintedanib and coated with polydopamine for adhering human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs-Exo) to synergistically harness their therapeutic effects. In vitro experiments demonstrated that the composite drug-loaded nanoparticles PNP@Exo significantly reduced the expression of inflammatory factors, COLI, and COL-III in bleomycin (BLM) induced A549 cells. Furthermore, administration of PNP@Exo into BLM-induced PF mice via nebulization significantly inhibited the production of extracellular matrix components and improved lung function without inducing systemic toxicity. Additionally, PNP@Exo inhibited the ferroptosis process in both PF cells and mice models. In conclusion, the composite drug-loaded nanoparticles synthesized in this study demonstrated a significant therapeutic efficacy in both PF cells and animal models, providing a novel strategy for the treatment of pulmonary fibrosis.
    Keywords:  Drug delivery; Exosomes; Pulmonary fibrosis
    DOI:  https://doi.org/10.1016/j.nano.2026.102925
  13. ACS Nano Med. 2026 Feb 20.
    Engineering Optimized EV-Mimetic Carriers for Efficient Tumor-Targeted Delivery of Functional RNA Nanoparticles.
    Nathalia Leal Dovaizem, Laura P Rebolledo, Anh Ha, Roger Chammas, Luciana Nogueira de Sousa Andrade, Kirill A Afonin.
      The therapeutic potential of RNAi is limited by the lack of safe, scalable, and efficient delivery systems. Although extracellular vesicles (EVs) are promising carriers for RNA therapeutics, poor scalability and low cargo-loading efficiency constrain their clinical translation. Here, we introduce fully synthetic EV-mimetic (EVM) carriers for the delivery of RNAi-inducing RNA nanoparticles to tumor cells. We systematically evaluated four different EVM cargo-loading strategies using representative RNA nanoparticles and appropriate controls. For each strategy, EVM size, concentration, and cargo encapsulation efficiency were assessed. Cellular uptake and RNA delivery were examined in melanoma 3D spheroids and compared with natural tumor-derived EVs, with EVMs demonstrating superior delivery efficiency. Functional RNAi activation was evaluated in tumor monolayers and 3D spheroids, where EVMs exhibited effective gene silencing with lower toxicity than conventional lipid-based carriers. Overall, our findings establish EVMs as safe and scalable biomimetic platforms for therapeutic nucleic acid delivery and identify optimal loading strategies and RNA nanoparticle designs for achieving maximal gene-silencing.
    Keywords:  EV Mimetics; Extracellular Vesicles; New Approach Methodologies; Nucleic Acid Nanoparticles; RNAi
    DOI:  https://doi.org/10.1021/acsnanomed.6c00004
  14. Stem Cell Res Ther. 2026 Mar 10.
    Engineering MSC-exosomes for diabetic bone regeneration: from mechanism to delivery.
    Guangmei Ran, Hongrui Jin, Qian Yang, Wentao Zhai, Jun Lu, Wenjie Jiang, Jingjing Luo, Shichang Fang, Yinchang Zhang, Huan Liu, Jian Zuo, Jiating Lin.
      The rapidly growing diabetic population is at high risk of dental implant failure due to a disrupted peri-implant immune microenvironment. Mesenchymal stem cells-derived exosomes (MSC-Exos) have emerged as a potent nanotherapeutic platform to remodel this hostile niche. Their mechanisms involve reprogramming macrophage polarization to alleviate inflammation, delivering pro-angiogenic miRNAs to restore vascular-osteogenic coupling, and modulating neuro-immune crosstalk to reestablish homeostasis. Collectively, these actions break the vicious cycle of impaired healing. Furthermore, engineering strategies such as membrane modification, integration with biomaterials, and preconditioning of parent cells can enhance the targeting, stability, and controlled release of MSC-Exos, thereby improving osseointegration outcomes in diabetic models. These engineering innovations, which focus on precise delivery and controlled release, are as critical to therapeutic development as elucidating the underlying biological mechanisms. This review systematically delineates the mechanisms by which MSC-Exos recalibrate the diabetic bone immune niche to foster osseointegration and critically discusses the clinical translation prospects of engineered exosome-based therapies.
    Keywords:  Bone immune microenvironment; Dental implant osseointegration; Diabetes; Exosome; Mesenchymal stem cell
    DOI:  https://doi.org/10.1186/s13287-026-04957-y
  15. J Nanobiotechnology. 2026 Mar 08.
    Microneedle-based delivery of cell membrane vesicles as IL-17RA decoys for Psoriasis treatment.
    Bin Tu, Weifeng Fang, Lin Liu, Yao Sun, Mei Hu, Akmal Asrorov, Zhao Wang, Ergang Liu, Yongzhuo Huang, Zhongqiu Liu, Weibo Dai.
      The dysregulation of IL-17/IL-17 receptor A (IL-17RA) signaling axis is a central driver of multiple autoimmune diseases. In contrast to targeting individual IL-17 cytokines, blocking IL-17RA simultaneously inhibits the receptor engagement of multiple IL-17 ligands, thereby effectively suppressing downstream pathway activation. Brodalumab, the only approved IL-17RA-blocking antibody, suggests robust clinical efficacy. However, its inhibition of IL-17RA has been associated with an increase in systemic IL-17 C levels, which is related to suicidal ideation and behavior. Consequently, the development of novel strategies capable of broadly blocking IL-17 signaling remains critically important. This study developed a novel therapeutic strategy by engineering cell-membrane vesicles with IL-17RA (IL-17RA-CMVs) as high-avidity decoy receptors for effectively blocking the IL-17/IL-17 receptor A (IL-17RA) signaling axis. Stable 293T cell lines exhibiting high surface expression of mouse or human IL-17RA (m/hIL-17RA), mediated by a platelet-derived growth factor receptor (PDGFR) transmembrane domain, were successfully constructed and applied for the preparation of m/hIL-17RA-CMVs. The mIL-17RA-CMVs were efficiently loaded into hyaluronic acid-based microneedles (mIL-17RA-CMVs-MNs), and the resulting mIL-17RA-CMVs-MNs exhibited sufficient mechanical strength to penetrate the skin and rapidly dissolved within 5 min upon insertion. In an imiquimod (IMQ)-induced murine psoriasis model, the topical application of mIL-17RA-CMVs-MNs significantly alleviated disease severity, as evidenced by a remarkable reduction in Psoriasis Area and Severity Index (PASI) scores, suppression of epidermal hyperplasia, and normalization of spleen index. Mechanistic studies revealed that the treatment mIL-17RA-CMVs-MNs markedly downregulated the expression of key IL-17RA pathway-related inflammatory mediators (CXCL1, CXCL2, CCL20) and antimicrobial peptides (S100A7/A8/A9) in skin lesions. Furthermore, in vitro experiments indicated that hIL-17RA-CMVs effectively functioned as decoy receptors, neutralizing IL-17 A and consequently inhibiting the upregulation of pro-inflammatory cytokines and hyperproliferation in HaCaT keratinocytes. This study presents a pioneering approach that synergizes the broad-spectrum neutralization capability of engineered decoy receptor vesicles with the localized and minimally invasive delivery advantage of microneedles. These findings position IL-17RA-CMVs (or IL-17RA-CMVs-MNs) as a highly promising and translatable therapeutic modality for the treatment of psoriasis and potentially other IL-17-mediated inflammatory diseases.
    Keywords:  Cell-membrane vesicles; Decoy receptor; IL-17RA; Microneedles; Psoriasis
    DOI:  https://doi.org/10.1186/s12951-026-04265-w
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