bims-engexo Biomed News
on Engineered exosomes
Issue of 2026–03–08
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. MicroRNA-493-5p engineered exosomes delivered via piezoelectric microneedles for epigenetic modulation of macrophages in diabetic wound healing.
  2. Harnessing Hitchhikers: Outer Membrane Vesicles Leading the Way in Advanced Cancer Therapeutics and Diagnostic- A Review.
  3. Engineered exosomes mediated siNox4 delivery loaded polyzwitterionic hydrogel with electrophysiologic conductivity for synergistic treatment of spinal cord injury via suppressing neuronal ferroptosis.
  4. Internal Loading of Environmentally Friendly InP/ZnSe/ZnS QDs in Bovine Milk Exosomes.
  5. Extracellular vesicles from IL-18-overexpressing and/or TGF-β1-deprived tumor cells as an immunogenic antigen source for next-generation DC vaccines.
  6. Engineered extracellular vesicles from human placental mesenchymal stem cells attenuate abdominal aortic aneurysm formation by inhibiting Nat10-mediated vascular smooth muscle cell senescence.
  7. Synergistic delivery of ginseng exosomes and biomimetic melanosomes via temporally controlled hydrogel microneedles restrain the pathologic triad of vitiligo.
  1. Mater Today Bio. 2026 Apr;37 102931
    MicroRNA-493-5p engineered exosomes delivered via piezoelectric microneedles for epigenetic modulation of macrophages in diabetic wound healing.
    Tao Chen, Lizhi Ouyang, Bobin Mi, Yishen Sheng, Fawwaz Al-Smadi, Hui Xu, Yaosen Wu, Xiaolei Zhang, Kailiang Zhou, Aimin Wu, Xiangyang Wang, Guohui Liu, Wenqian Zhang.
      Diabetic foot ulcers, affecting millions worldwide, face impaired healing due to dysregulated macrophage polarization. However, the epigenetic mechanisms underlying aberrant macrophage polarization remain to be elucidated. This study introduces a multifunctional, exosome-based delivery platform that combines miR-493-5p-engineered M2 macrophage exosomes with piezoelectric GelMA microneedles to reprogram macrophage metabolism and epigenetics for diabetic wound healing. Engineered EXO@miR-493-5p are embedded in GelMA microneedles (MN) and delivered via a ZnO piezoelectric substrate with a nanosilver/GOx coating to provide antibacterial and antioxidant benefits. Ultrasound-induced electrostimulation enhances exosome deposition and endocytic uptake, enabling sustained, localized cargo release. Mechanistically, miR-493-5p targets HDAC1 to amplify histone H3K18 lactylation, activating the STAT6 axis and driving metabolic reprogramming toward M2 polarization with upregulation of Arg1. In vitro, EXO@miR-493-5p promote M2 markers and angiogenesis. In vivo, they accelerate wound closure, promote re-epithelialization, collagen deposition, and neovascularization, while reducing ROS and inflammation. The integrated platform offers a translatable, epigenetic-metabolic strategy for chronic diabetic wounds.
    DOI:  https://doi.org/10.1016/j.mtbio.2026.102931
  2. Cancer Lett. 2026 Feb 26. pii: S0304-3835(26)00133-3. [Epub ahead of print] 218370
    Harnessing Hitchhikers: Outer Membrane Vesicles Leading the Way in Advanced Cancer Therapeutics and Diagnostic- A Review.
    Farzaneh Sharifzad, Amirhossein Sharifzad, Praveen Thumbikat, Helia Purnaghshband, Ali Ghamari, Golnaz Vaseghi, Amir Mahmoodzadeh, Marjan Assefi, Marek J Los, Saeid Ghavami.
      Cancer therapy is increasingly shaped by delivery platforms designed to overcome the limitations of conventional chemotherapy and radiotherapy. Among these, bacterial outer membrane vesicles (OMVs) have emerged as versatile nanocarriers with intrinsic tumor-interacting properties, immunomodulatory capacity, and amenability to bioengineering. Their lipid bilayer composition not only enhances stability and cellular uptake but also intersects with tumor lipid metabolism-an axis increasingly recognized as central to oncogenesis, immune evasion, and therapeutic resistance. Here, we review mechanistic links between OMV lipid composition and autophagy regulation and discuss how engineered OMVs can be used to modulate tumor metabolism, immune responses, and therapy sensitivity. By influencing lipid-autophagy crosstalk, OMVs function as more than passive delivery vehicles; they can actively engage intracellular stress pathways and metabolic dependencies. Autophagy, a context-dependent regulator of cancer survival and suppression, is particularly relevant, as OMVs can deliver bioactive lipids, proteins, or nucleic acids that either promote immunogenic stress responses or attenuate tumor-protective autophagy. Preclinical examples-including doxorubicin-loaded OMVs and PD-1-engineered OMVs-illustrate how these principles translate into enhanced anti-tumor efficacy and immune activation. We further discuss how integration with lipidomics, systems biology, and artificial intelligence-guided design may improve OMV engineering and therapeutic predictability. Collectively, these advances position OMVs as a promising, though still emerging, platform for precision oncology.
    Keywords:  Autophagy; Cancer Therapy; Drug Delivery; Exosomes; Outer membrane vesicle; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.canlet.2026.218370
  3. Biomaterials. 2026 Feb 27. pii: S0142-9612(26)00120-1. [Epub ahead of print]331 124096
    Engineered exosomes mediated siNox4 delivery loaded polyzwitterionic hydrogel with electrophysiologic conductivity for synergistic treatment of spinal cord injury via suppressing neuronal ferroptosis.
    Chenyu Wu, Yueman Tang, Zhichen Jiang, Chenglong Hong, Qi Yang, Zhouwei Wu, Jiangwei Zhu, Kaijie Guo, Jiang Liu, Si Yu Zheng, Lei Guo, Hui Xu, Wenfei Ni, Xiangyang Wang, Sunren Sheng, Jian Xiao, Chenggui Wang.
      
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.124096
  4. ACS Omega. 2026 Feb 24. 11(7): 12799-12809
    Internal Loading of Environmentally Friendly InP/ZnSe/ZnS QDs in Bovine Milk Exosomes.
    Minji Ko, Hansol Lee, Heejin Jung, Keyong Nam Lee, Sekyoo Jeong, Young Kwang Lee, Young Rag Do.
      To enable stable and reliable fluorescence tracking in biological environments, this study presents a highly efficient, cadmium-free, and eco-friendly platform for exosome labeling using InP/ZnSe/ZnS quantum dots (QDs). QDs, known for high efficiency, were synthesized using a hot-injection method. To ensure water dispersibility and biocompatibility, the QD oleic acid (OA) surface ligands were sequentially exchanged with 11-mercaptoundecanoic acid (MUA) and polyethylene glycol (PEG) to internalize of QDs within exosomes. Structural unchangeable bovine milk-derived exosomes were purified for exosome internalization using electrophoretic oscillation-assisted tangent flow filtration (EPOTF) with 200 nm SiN x nanofilters. Ultrasonic treatment was optimized to internalize QDs into exosomes without causing structural deformation, which was confirmed by TEM imaging. The resulting QD-exosomes retained 89% of their initial photoluminescent intensity under continuous laser exposure, in contrast to a significant drop to 10% for conventional PKH67-labeled exosomes. Confocal microscopy demonstrated efficient uptake of QD-exosomes into HaCaT cells and distinct localization around the nucleus. This approach, which integrates eco-friendly QD synthesis, exosome-compatible surface modification, structurally unchangeable ultrasonic embedding, and dual-stage purification, provides a robust and scalable strategy for bioimaging and is suitable for real-time imaging, targeted drug delivery, and advanced nanomedicine applications.
    DOI:  https://doi.org/10.1021/acsomega.5c13609
  5. J Control Release. 2026 Mar 02. pii: S0168-3659(26)00173-2. [Epub ahead of print] 114771
    Extracellular vesicles from IL-18-overexpressing and/or TGF-β1-deprived tumor cells as an immunogenic antigen source for next-generation DC vaccines.
    Joanna Rossowska, Daria Nawrocka, Bożena Szermer-Olearnik, Michalina Pęcherz, Anas Waer-Asea, Paweł Karpiński, Michał Tracz, Magdalena Milczarek.
      Dendritic cell (DC)-based antitumor immunotherapies have demonstrated significant therapeutic potential. Nonetheless, their broader clinical application is limited for several reasons, including the lack of comprehensive sources of tumor antigens. Tumor-derived extracellular vesicles (TEVs) provide a rich source of tumor-associated antigens. However, unmodified TEVs, due to the high levels of immunosuppressive molecules, inhibit processes related to antigen processing and their presentation to naïve T lymphocytes. This study aimed to engineer TEVs via lentiviral modification of parental colon carcinoma MC38 cells to overexpress IL-18 and/or shRNA targeting IL-10 or TGF-β1 to enhance the immunogenic potential of TEVs. The modified TEVs were characterized with TEM, Western blotting, ELISA, and RT-qPCR. Functional activity was tested in vitro using flow cytometry and confocal imaging. In vivo studies used a C57BL/6 syngeneic MC38 tumor model. mTEVs from MC38 cells engineered to overexpress IL-18 and/or silence TGF-β1 strongly stimulated DCs, triggering a potent, multifaceted antitumor response in vitro and in vivo. The combination of both modifications exerted an additive effect, enhancing the therapeutic efficacy of DCs and significantly inhibiting tumor growth. In addition to altering cytokine levels, genetic modifications also changed the vesicle's miRNA and protein cargo, potentially boosting their immunostimulatory role. Our findings provide compelling evidence that rational genetic engineering of tumor cells can effectively transform the extracellular vesicles they produce, shifting their immunosuppressive, tumor-supporting potential into an immunogenic one. Interleukin-18-loaded and TGF-β1-deprived TEVs can serve as a highly versatile and naturally immunogenic platform for the next-generation DC-based anticancer vaccines.
    Keywords:  Dendritic cell-based immunotherapy; Interleukin 18; MC38; Transforming growth factor β1; Tumor-derived extracellular vesicles; colon carcinoma
    DOI:  https://doi.org/10.1016/j.jconrel.2026.114771
  6. Biomaterials. 2026 Feb 27. pii: S0142-9612(26)00133-X. [Epub ahead of print]331 124109
    Engineered extracellular vesicles from human placental mesenchymal stem cells attenuate abdominal aortic aneurysm formation by inhibiting Nat10-mediated vascular smooth muscle cell senescence.
    Xiaoqian Jia, Xiao Hu, Ziwei Fu, Liwen Zhang, Xiajing Luo, Weichi Huang, Yuhao Hua, Qin Fang, Jincai Zeng, Fuwen Huang, Guoquan Wei, Jianping Bin, Hao Zheng, Guojun Chen, Senlin Huang.
      Human placental mesenchymal stem cell-derived extracellular vesicles (hPMSC-EVs) have demonstrated anti-senescence effects across various diseases. However, their role in abdominal aortic aneurysm (AAA), a degenerative aortic pathology, remains unexplored. Our findings demonstrated that hPMSC-EVs effectively delay vascular smooth muscle cell (VSMC) senescence. In vivo, modification of hPMSC-EVs with an osteopontin(OPN)-targeted peptide facilitated precise homing to aneurysmal sites and improved local retention. Additionally, administration of OPN-targeted hPMSC-EVs significantly reduced AAA formation in both AngII and elastase-induced murine models, by inhibiting VSMC senescence. Mechanistic studies further demonstrated that hPMSC-EVs suppressed VSMC senescence and lowered AAA incidence through downregulation of Nat10 expression. MiRNA sequencing identified miR-149-5p encapsulated in hPMSC-EVs as the key mediator of Nat10 suppression. These results position OPN-targeted hPMSC-EVs as a promising targeted therapy for AAA, exerting protective effects via the miR-149-5p/Nat10/senescence axis.
    Keywords:  Abdominal aortic aneurysm; Extracellular vesicle; Human placental mesenchymal stem cell; Senescence; Vascular smooth muscle cell
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.124109
  7. J Nanobiotechnology. 2026 Mar 02.
    Synergistic delivery of ginseng exosomes and biomimetic melanosomes via temporally controlled hydrogel microneedles restrain the pathologic triad of vitiligo.
    Luyue Chang, Junqi Xiang, Ting Zhang, Yanna Ban, Lihua Kang, Yujuan Wu, Li Du, Shasha Zhu, Yao Gong, Xiaoying Zhang, Li Wang, Jin Chen, Wei Cheng, Jie Xu.
      Vitiligo pathogenesis involves progressive melanocyte loss and keratinocyte dysfunction, which are driven primarily by oxidative stress resulting from excessive ROS accumulation. We engineered a temporally controlled hydrogel microneedle system that integrates ginseng-derived exosomes (G-Exos) with biomimetic polydopamine nanoparticles (PDA@PEGs) to concurrently target the pathogenic triad of vitiligo, including oxidative stress, inflammation, and melanocyte deficiency. This system employs methacrylated hyaluronic acid (HAMA) hydrogel microneedles for rapid PDA@PEG release while utilizing glyceryl monostearate micelles to achieve matrix metalloproteinase-9 (MMP-9)-responsive G-Exo release at inflammatory foci, enabling intelligent spatiotemporal control. Functionally, G-Exos help restore redox homeostasis and suppress inflammation through bioactive constituents, thereby protecting melanocytes and enhancing keratinocyte proliferation. Moreover, PDA@PEG promotes repigmentation through the dual mechanisms of exogenous melanin deposition and endogenous melanogenesis stimulation. In murine models, this strategy achieves significant repigmentation within 3 weeks by activating follicular stem cells, upregulating melanogenic markers (Tyr/Mc1r), increasing antioxidant defense (ApoE), and suppressing inflammatory signaling (IL-17). This natural-biomimetic hybrid design leverages biocompatible materials to co-target multiple pathological axes, offering a novel self-adaptive approach for microenvironmental rehabilitation in vitiligo.
    Keywords:  Ginseng-derived exosomes; Hydrogel microneedles; Oxidative stress; Repigmentation; Vitiligo
    DOI:  https://doi.org/10.1186/s12951-026-04168-w
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