bims-engexo Biomed News
on Engineered exosomes
Issue of 2025–03–02
nine papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. TAM-derived exosomal miR-589-3p accelerates ovarian cancer progression through BCL2L13.
  2. Tetrahedral-DNA-Nanostructure-Modified Engineered Extracellular Vesicles Enhance Oral Squamous Cell Carcinomas Therapy by Targeting GPX4.
  3. Physical characterization of PEGylated exosome constructs: Size, charge, and morphology changes in non-specific alkylating N-terminal reactions.
  4. Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models.
  5. Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury.
  6. Biology, Pathology, and Targeted Therapy of Exosomal Cargoes in Parkinson's Disease: Advances and Challenges.
  7. A one-two punch of inflammation and oxidative stress promotes revascularization for diabetic foot ulcers.
  8. A self-adjuvant multiantigenic nanovaccines simultaneously activate the antiviral and antitumor immunity for the treatment of cancers.
  9. Enhanced human adipose-derived stem cells with VEGFA and bFGF mRNA promote stable vascular regeneration and improve cardiac function following myocardial infarction.
  1. J Ovarian Res. 2025 Feb 21. 18(1): 36
    TAM-derived exosomal miR-589-3p accelerates ovarian cancer progression through BCL2L13.
    Jianqing Wang, Yan Zhu, Yang He, Weiwei Shao.
       BACKGROUND: Tumor-associated macrophages (TAM) are critical elements of intercellular communication in tumor microenvironment (TME), and exosomes are key mediators between tumor cells and the TME. According to previous reports, miRNAs exert a pivotal role in ovarian cancer (OC) development. The purpose of this work was to explore the function of TAM-derived exosomal miR-589-3p in OC development and elucidate the underlying molecular mechanisms.
    METHODS: First, peripheral blood mononuclear cells (PBMC) were treated with IL-4 and IL-13 to polarize them into M2-type macrophages. Exosomes were separated from M2-type macrophages, and the physical properties of exosomes were evaluated using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Next, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was applied to examine the expression of relevant genes. Subsequently, Targetscan and miRDB were utilized to predict miR-589-3p target genes, and then the interaction between miR-589-3p and BCL2L13 was verified by dual luciferase assay and RNA Binding Protein Immunoprecipitation (RIP) assay. Finally, Cell Counting Kit-8 (CCK-8) and flow cytometry experiments were employed to explore the changes in the proliferative and apoptotic abilities of OC cells.
    RESULTS: In this research, we demonstrated that TAM-derived exosomes facilitated OC cell proliferation and suppressed OC cell apoptosis. Then, qRT-PCR results indicated that miR-589-3p were markedly elevated after co-culture of TAM-derived exosomes with OC cells. In addition, we discovered that miR-589-3p was bound to BCL-2-like protein 13 (BCL2L13), which was confirmed through luciferase assay and RIP assay. Furthermore, functional analysis displayed that TAM-derived exosomes treated with miR-589-3p inhibitor attenuated the promotion of OC cell progression by exosomes.
    CONCLUSION: TAM-derived exosomal miR-589-3p enhanced OC progression through BCL2L13, which offers a novel for OC therapy.
    Keywords:  BCL2L13; Exosome; OC; TAM; miR-589-3p
    DOI:  https://doi.org/10.1186/s13048-025-01618-1
  2. ACS Nano. 2025 Feb 27.
    Tetrahedral-DNA-Nanostructure-Modified Engineered Extracellular Vesicles Enhance Oral Squamous Cell Carcinomas Therapy by Targeting GPX4.
    Dianri Wang, Yun Wang, Sicheng Zhang, Xueting Yang, Yan Yang, Teng Han, Yi Luo, Chunyan Shui, Mu Yang, Yunfeng Lin, Chao Li.
      Oral squamous cell carcinoma (OSCC) represents a heterogeneous group of malignancies originating from the mucosal lining of the oral cavity. Current treatment modalities primarily involve surgery, chemotherapy, and radiotherapy. Despite the use of multimodal therapy, the 5 year overall survival rate for OSCC remains around 50%, underscoring the need for the development of nontoxic agents with potent antitumor activity. Extracellular vesicles (EVs) are nanoscale, membrane-bound structures that can selectively deliver small molecules, nucleic acids, and proteins to target cells, making them a promising platform for drug delivery in cancer therapy. Strategies to improve the uptake of EVs and enhance the delivery of therapeutic molecules to target cells are critical for advancing precision medicine. Tetrahedral DNA nanostructures (TDNs) have shown significant potential in facilitating drug endocytosis and delivery, as well as improving tissue penetration. In this study, TDN@EVs were conducted by modifying the membrane surface of M1-EVs with TDNs, which demonstrated improved biological stability and drug delivery efficiency compared to unmodified EVs. In vitro and in vivo experiments showed that TDN@EVs significantly inhibited OSCC cell proliferation and migration while promoting apoptosis. TDN@EVs exhibited superior drug penetration properties, further amplifying their antitumor effects. Proteomic analysis identified Hsc70 as the key protein responsible for the antitumor activity of the TDN@EVs. The efficient delivery of Hsc70 into tumor cells by TDN@EVs led to the degradation of GPX4, inducing ferroptosis, mitochondrial stress, and DNA damage in tumor cells. These findings highlight the potential of TDN@EVs as an effective and safe approach for cancer therapy. In conclusion, TDN@EVs present as a promising effective strategy for the targeted delivery of therapeutic agents in OSCC treatment, offering enhanced biological stability, efficient drug delivery, and significant antitumor effects.
    Keywords:  cancer treatments; extracellular vesicles; oral squamous cell carcinoma; tetrahedral framework nucleic acids
    DOI:  https://doi.org/10.1021/acsnano.5c00674
  3. J Biomater Appl. 2025 Feb 25. 8853282251323198
    Physical characterization of PEGylated exosome constructs: Size, charge, and morphology changes in non-specific alkylating N-terminal reactions.
    Andrés Martínez-Santillán, José González-Valdez.
      Small extracellular vesicles, commonly referred to as exosomes, withhold a promising future in the pharmaceutical industry as carriers for targeted drug delivery due to their high specificity and bioavailability when compared to synthetic-based vectors. They, however, present some limitations for systematic administration because of natural organism defenses and their high-water solubility, ultimately making it difficult for them to reach the intended target. To improve the delivery capacity of these nanoparticles, the possibility for the construction of PEGylated versions was explored in this work. This process was performed, analyzed, and characterized using N-terminal specific PEGylation reactions targeted to the protein contents in the exosomal membrane. For this, two different mono-methoxy polyethylene glycols (mPEG) of 5 and 20 kDa were reacted with exosomes under alkylating conditions. The resulting 5k and 20k PEGylated exosome constructs were characterized and compared with unmodified exosomes, using size, morphology, and zeta potential as comparison parameters. Results after analysis showed an absorbance reduction of approximately 65% and 34% (for the 5 and 20 kDa conjugates respectively), a reduction of 10 to 20% in peak resolution, particle size increase corresponding to the polymer sizes used, and a slight reduction in electric distribution of about 2 to 3 mV less than the unmodified vesicles. The data obtained may provide insights for the optimization of exosome PEGylation strategies for therapeutic use.
    Keywords:  Exosomes; PEG; PEGylation; extracellular vesicles; size-exclusion chromatography
    DOI:  https://doi.org/10.1177/08853282251323198
  4. Pharmaceutics. 2025 Feb 17. pii: 264. [Epub ahead of print]17(2):
    Engineered Exosomes Carrying Super-Repressor IκB Reduced Biliary Atresia-Induced Liver Fibrosis in Minipig and Mouse Models.
    Jisoo Kang, Cheolhyoung Park, Hanoul Yun, Chulhee Choi, Wonhyo Seo.
      Background and Aim: Biliary atresia is a rare, progressive disease that affects the bile ducts in newborns. Persistent bile duct obstruction induces various pathological conditions, including jaundice, inflammation, and liver fibrosis; however, the exact pathogenesis of biliary atresia is not yet fully understood. Nuclear factor-κB (NF-κB) is widely acknowledged as a key regulator in the pathogenesis of hepatitis and liver fibrosis, and extensive research has been conducted to develop strategies to effectively inhibit its activity to mitigate liver damage. Exosome-based therapeutic platforms offer targeted NF-κB inhibition with low immunogenicity and enhanced liver-specific delivery. This study aimed to evaluate the therapeutic efficacy of Exo-SrIκB in treating cholestatic liver fibrosis using experimental animal models. Methods: Exo-SrIκB (an exosome-based therapy containing the super-repressor IκB protein) using EXPLOR technology (Exosome engineering for Protein Loading via Optically Reversible protein-protein interactions) to encapsulate the super repressor IκB (SrIκB) within exosomes. The therapeutic efficacy of Exo-SrIκB was assessed in minipig and mouse models with experimentally induced cholestatic liver disease. Results: Administration of Exo-SrIκB significantly attenuated liver fibrosis progression in both animal models by inhibiting NF-κB nuclear translocation and reducing the expression of fibrotic markers. Treated animals exhibited reduced collagen deposition, lower α-SMA levels, and improved hepatic function compared to untreated controls. Conclusion: Exo-SrIκB effectively suppressed NF-κB signaling and alleviated liver fibrosis in experimental cholestatic liver disease models, suggesting that exosome-based therapeutics may offer a targeted and biocompatible application to managing liver fibrosis and other chronic liver diseases.
    Keywords:  biliary atresia; engineered exosome; liver fibrosis; super-repressor IκB
    DOI:  https://doi.org/10.3390/pharmaceutics17020264
  5. J Nanobiotechnology. 2025 Feb 22. 23(1): 134
    Engineered neutrophil membrane-camouflaged nanocomplexes for targeted siRNA delivery against myocardial ischemia reperfusion injury.
    Yaohui Jiang, Rongyan Jiang, Zequn Xia, Meng Guo, Yanan Fu, Xiaocheng Wang, Jun Xie.
      Small interfering RNA (siRNA) therapies hold great potential for treating myocardial ischemia-reperfusion injury (MIRI); while their practical application is limited by the low bioavailability, off-target effects, and poor therapeutic efficacy. Here, we present an innovative engineered neutrophil membrane-camouflaged nanocomplex for targeted siRNA delivery and effective MIRI therapy. A nanoparticle (NP)-based siRNA delivery system, namely MNM/siRNA NPs, is camouflaged with neutrophil membranes modified by hemagglutinin (HA) and integrins. Our comprehensive in vitro studies show that MNM/siRNA NPs effectively facilitate endosomal escape through HA, achieve excellent targeting via integrins, and significantly reduce integrin α9 expression. Furthermore, in MIRI mice, we identify integrin α9 as a potential target for MIRI therapy and demonstrate that MNM/siRNA NPs significantly decrease myocardial infarction area and improve cardiac function by reducing neutrophil recruitment, neutrophil extracellular trap (NET) and microthrombus formation. These findings highlight the engineered membrane-camouflaged NPs as a promising siRNA delivery platform, offering an effective treatment strategy for MIRI.
    Keywords:  Engineered neutrophil membrane; Integrin α9; Myocardial ischemia-reperfusion injury; Neutrophils; siRNA
    DOI:  https://doi.org/10.1186/s12951-025-03172-w
  6. Mol Neurobiol. 2025 Feb 25.
    Biology, Pathology, and Targeted Therapy of Exosomal Cargoes in Parkinson's Disease: Advances and Challenges.
    Faezeh Almasi, Faeze Abbasloo, Narges Soltani, Masoud Dehbozorgi, Atousa Moghadam Fard, Arash Kiani, Nasim Ghasemzadeh, Hassan Mesgari, Elaheh Zadeh Hosseingholi, Zahra Payandeh, Parjin Rahmanpour.
      Parkinson's disease (PD) involves the loss of dopamine neurons and accumulation of alpha-synuclein (α-syn), leading to Lewy bodies. While α-syn-targeting immunotherapies show promise, clinical application is challenging. Emerging strategies include nano-platforms for targeted delivery and imaging, and cell-based therapies with patient-specific dopaminergic neurons, aiming to enhance treatment effectiveness despite challenges. Exosome-based methodologies are emerging as a promising area of research in PD due to their role in the spread of α-syn pathology. Exosomes are small extracellular vesicles that can carry misfolded α-syn and transfer it between cells, contributing to the progression of PD. They can be isolated from biological fluids such as blood and cerebrospinal fluid, making them valuable biomarkers for the disease. Additionally, engineering exosomes to deliver therapeutic agents, including small molecules, RNA, or proteins, offers a novel approach for targeted therapy, capitalizing on their natural ability to cross the blood-brain barrier (BBB). Ongoing studies are evaluating the safety and efficacy of these engineered exosomes in clinical settings. This review explores the role of exosomes in PD, focusing on their potential for diagnosis, treatment, and understanding of pathology. It highlights advancements and future directions in using exosomes as biomarkers and therapeutic tools.
    Keywords:  Alpha-synuclein; Exosomes; MicroRNA; Parkinson’s disease; Theranostic strategies
    DOI:  https://doi.org/10.1007/s12035-025-04788-7
  7. Mater Today Bio. 2025 Apr;31 101548
    A one-two punch of inflammation and oxidative stress promotes revascularization for diabetic foot ulcers.
    Li Chen, Yunrong Li, Xuanxuan Zhang, Lixin Ma, Cheng Zhang, Huanhuan Chen.
      Patients with diabetic foot ulcers (DFU) suffering from severe lower limb ischemia face the risk of amputation. Concomitant oxidative stress and hyperinflammation commonly manifest within the tissue affected by DFU, exacerbating the deterioration of DFU wounds. One-two punch strategy of anti-oxidative damage plus anti-inflammatory is anticipated to tackle the challenge of non-healing diabetic wounds. Here, we introduced a dual-approach treatment strategy involving the probiotic Weissella cibaria (WC) modified with desferrioxamine (DFO). This engineered probiotic, known as WC@DPA, aims to ameliorate oxidative stress within the ischemic microenvironment and stimulate the formation and proliferation of endothelial tubular structures. When applied with chronic wounds and ischemic hindlimb injuries in diabetic mice, WC@DPA gel demonstrated an effective performance in modulating oxidative damage, reducing local vascular inflammation, and facilitating muscle tissue repair and vascular reconstruction. We believe that our engineered probiotic represents a promising therapeutic avenue for managing ischemic injuries associated with DFU.
    Keywords:  Angiogenesis; Anti-inflammation; Engineered living materials; Nitric oxide; Wound healing
    DOI:  https://doi.org/10.1016/j.mtbio.2025.101548
  8. J Nanobiotechnology. 2025 Feb 27. 23(1): 150
    A self-adjuvant multiantigenic nanovaccines simultaneously activate the antiviral and antitumor immunity for the treatment of cancers.
    Zhongjie Wang, Hanlin Chen, Ruiqi Ming, Weiwei Wang, Shujun Liu, Yuantian Jing, Zewei Yan, Guihong Lu, Li-Li Huang.
       BACKGROUND: Tumor cell-derived extracellular vesicles (tEVs) have garnered significant attention as promising antigen delivery vehicles for the development of cancer vaccines. However, their practical applications are hindered by weak immunogenicity and inadequate lymph node targeting. In this study, we engineered tEVs into "self-adjuvant" multiantigenic nanovaccines that simultaneously accumulate in tumors and lymph nodes (LNs), effectively triggering innate and adaptive immunity capable of recognizing both tumor cells and virus antigen-modified tumor cells to inhibit tumor progression.
    RESULTS: 4T1 tumor cells were infected with vesicular stomatitis virus (VSV), leading to the expression of VSVG and calreticulin (CRT) on their surface. Using these infected cells, we prepared extracellular vesicles (vEVs) carrying both VSVG and CRT. When injected subcutaneously, vEVs targeted tumors effectively due to the homologous targeting capability of tumor cell membranes. In which, VSVG induced fusion between vEVs and tumor cells, creating viral antigen-decorated tumor cells, which enhanced the recognition and phagocytosis of tumor cells by macrophages. Additionally, the surface CRT of vEVs activated the "eat-me" signaling, thus improving their recognition and uptake by dendritic cells (DCs). This led to DC maturation and the activation of antiviral and antitumor T cells, synergistically inhibiting tumor growth.
    CONCLUSIONS: This research introduces a straightforward yet efficacious methodology for the production of cancer vaccines to fight cancer through the stimulation of both the antiviral and antitumor immune responses within the body.
    Keywords:  Antiviral and antitumor immunity; Cancer immunotherapy; Low pH-responsive; Lymph node–tumor dual-targeting; Multiantigenic nanovaccine
    DOI:  https://doi.org/10.1186/s12951-025-03208-1
  9. Clin Transl Med. 2025 Mar;15(3): e70250
    Enhanced human adipose-derived stem cells with VEGFA and bFGF mRNA promote stable vascular regeneration and improve cardiac function following myocardial infarction.
    Kaixiang Li, Runjiao Luo, Xindi Yu, Wei Dong, Guoliang Hao, Dan Hu, Ziyou Yu, Minglu Liu, Tingting Lu, Xiangying Wang, Xin Tang, Xinjun Lin, Huijing Wang, Wei Wang, Wei Fu.
      Mesenchymal stem cell therapy involves the secretion of various factors to regulate the local microenvironment in various of diseases. This therapy offers hope for treating acute myocardial infarction (MI), which poses a serious threat to human health. However, challenges such as low paracrine efficiency and poor cell survival persist due to the harsh post-infarction conditions, such as hypoxia. Recently, enhanced cell therapy, in which vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) are used as therapeutic agents to limit myocardial injury and simultaneously induce neovascularisation, has been recognised as a promising new strategy to improve the efficacy of cell therapy. Chemically synthetic modified messenger RNA (modRNA), a novel protein expression technology, enables safe, rapid, efficient and pulsatile expression of target proteins in vivo and in vitro settings. It has been widely applied in the fields of vaccine research and tissue regeneration. In this study, human adipose-derived stem cells (hADSCs) were transfected with VEGFA and bFGF modRNA to transiently overexpress these proteins before transplantation. This modification enhanced the paracrine effect of transplanted hADSCs and promoted stability in the vascular network at the transplantation site. Overexpression of VEGFA and bFGF in hADSCs not only inhibited apoptosis but also reduced ventricular remodelling and improved cardiac function and left ventricular conduction. Overall, the additive effects of VEGFA modRNA, bFGF modRNA and hADSCs hold promise for comprehensive cardiac repair post-MI and show substantial potential for treating ischemic heart diseases. KEY POINTS: ModRNAs-transfected hADSCs exhibit pulsed and transient expression, enabling efficient production of functional VEGFA and bFGF proteins. Intracardiac injection of these engineered hADSCs leads to the enhancement of cardiac function and the improvement of electrical conduction. The hADSCsdual mainly exerts its effect on myocardial infarction by promoting stable vascular regeneration and suppressing cell apoptosis.
    Keywords:  VEGF; bFGF; cell therapy; human adipose‐derived stem cell; modRNA; myocardial infarction
    DOI:  https://doi.org/10.1002/ctm2.70250
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