bims-engexo 2026-04-19 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–04–19
ten papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Exosomes derived from Bcl-2-engineered iPSC-cardiomyocytes mitigate aortic valve calcification and inhibit cardiomyocyte apoptosis.
Heme oxygenase-1-enriched tolerogenic dendritic cell-derived exosomes attenuate lupus nephritis by restoring immune balance and iron homeostasis.
Pirfenidone-exosomes as innovative strategies for scarless tissue repair in wound healing.
Engineering Extracellular Vesicles for Tumor Targeted Therapy: Source Optimization, Modification, and Clinical Application.
Therapeutic potential of ADAR1-regulated macrophage exosomes for improving myocardial damage in septic cardiomyopathy.
Tumor-targeted Exosomal Delivery of Celastrol for Enhanced Therapeutic Efficacy in NSCLC.
From Nature to Nanomedicine: Engineered Plant-Derived Nanovesicles for Skin Disease.
miR-4516-Loaded Engineered Milk Extracellular Vesicles Attenuate Indoxyl Sulfate-Induced Mitochondrial Dysfunction and Improve Renal Function in a CKD Mouse Model.
Engineered mesenchymal stem cell-derived extracellular vesicles attenuate acute glaucoma-induced neuroinflammation by reprogramming microglial polarization.
Selenized neural stem cell exosomes for CNS trauma repair.

Int J Pharm. 2026 Apr 13. pii: S0378-5173(26)00325-X. [Epub ahead of print] 126877

Exosomes derived from Bcl-2-engineered iPSC-cardiomyocytes mitigate aortic valve calcification and inhibit cardiomyocyte apoptosis.

Ni Li, Renyuan Xiao, Linwen Zhu, Liyan Cai, Zheng Zhang, Lebo Sun, Huoshun Shi, Honghua Ye, Guofeng Shao, Jianqing Gao.

  Calcific Aortic Valve Disease (CAVD) is a progressive cardiovascular disorder, the pathological processes of which are correlated with cell apoptosis, inflammatory response, and osteogenic remodeling of valve interstitial cells. Presently, there exists no effective pharmacological treatment or intervention to impede or reverse the advancement of this disease. Systematically identifying key molecular biomarkers and their regulatory pathways is crucial for the formulation of novel therapeutic strategies. Exosomes, functioning as a novel drug delivery system, can transport specific functional molecules. In this research, proteomic and transcriptomic analyses disclosed an imbalance in the bcl2/bax apoptosis regulatory axis in CAVD. Further exploration indicated that miR-132, which IL-1β regulates, is dysregulated and associated with increased cellular apoptosis. To re-establish homeostasis in apoptotic and inflammatory pathways, engineered exosomes overexpressing bcl2, derived from induced pluripotent stem cell-derived cardiomyocytes (iPSCbcl2-CM-Exos), were constructed. In vitro experiments demonstrated that iPSCbcl2-CM-Exos significantly diminished the apoptosis rate of cardiomyocytes and valve interstitial cells induced by H2O2. Modulations in apoptosis-related markers further supported their potential anti-apoptotic effect. In vivo, iPSCbcl2-CM-Exos are safe and effective. They upregulate bcl2, downregulate bax, restore miR-132 expression, and inhibit the abnormal elevation of IL-1β, thereby notably reducing the apoptosis of valve interstitial cells, enhancing cardiac function, and alleviating leaflet thickening and fibrosis. This study identifies an imbalance in the bcl2/bax axis as a key molecular characteristic of CAVD. It demonstrates that bcl2-engineered exosomes can simultaneously target apoptotic and inflammatory pathways, thereby presenting a promising cell-free therapeutic strategy for CAVD.

Keywords:  Apoptosis; Bcl2/bax; Calcific aortic valve disease; Exosomes; IL-1β; miR-132

DOI:  https://doi.org/10.1016/j.ijpharm.2026.126877
Free Radic Biol Med. 2026 Apr 10. pii: S0891-5849(26)00308-4. [Epub ahead of print]251 60-74

Heme oxygenase-1-enriched tolerogenic dendritic cell-derived exosomes attenuate lupus nephritis by restoring immune balance and iron homeostasis.

Zhouhang Xing, Jinlin Yang, Huan Zhang, Yuanyuan Xie, Qianru Yang, Min Wu, Wenqian Wang, Sheng Gao, Chunyan Hua.

  Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by chronic inflammation, oxidative stress, and multi-organ damage, with lupus nephritis (LN) constituting a major cause of morbidity and mortality. Dysregulated iron metabolism and insufficient expression of heme oxygenase-1 (HO-1), a pivotal antioxidant enzyme regulating iron homeostasis and immune responses, have been implicated in LN pathogenesis. However, therapeutic strategies targeting HO-1 and iron dysregulation remain underexplored. Here, we demonstrate that HO-1 expression is markedly decreased in peripheral blood mononuclear cells from SLE patients, particularly those with LN, correlating inversely with disease activity and markers of iron homeostasis disruption. We established that IL-10 induces tolerogenic dendritic cells (tolDCs) through activation of the Nrf2-HO-1 pathway, concomitant with modulation of iron metabolism and oxidative stress genes. Leveraging this mechanism, we generated HO-1-enriched tolDC-derived exosomes (HO-1high-tolDex) and characterized their immunomodulatory properties in vitro, showing effective suppression of pro-inflammatory cytokines and restoration of iron regulatory gene expression in recipient DCs. In vivo, HO-1high-tolDex administered intravenously preferentially accumulated in kidneys of lupus-prone mice, exhibiting superior stability and targeting compared to parental tolDCs. Repeated dosing ameliorated renal pathology, concomitant with decreased DC activation and pathogenic autoantibody titers. Importantly, HO-1high-tolDex reversed oxidative stress imbalances and normalized iron homeostasis markers, mitigating abnormal renal iron accumulation. These findings establish HO-1high-tolDex as a potent, novel cell-free therapeutic agent that simultaneously modulates immune dysregulation, oxidative stress, and iron metabolism in SLE.

Keywords:  Dendritic cell-derived exosome; Heme oxygenase-1; Lupus nephritis; Systemic lupus erythematosus; Tolerogenic dendritic cell

DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.04.024
Drug Deliv Transl Res. 2026 Apr 13.

Pirfenidone-exosomes as innovative strategies for scarless tissue repair in wound healing.

Jin Wang, Chen Sun, Emmanuel A Ho.

  To facilitate scarless wound healing, developing an anti-scarring treatment that modulates dermal fibroblast activity is a promising strategy, with pirfenidone (PFD) showing potential due to its anti-fibrotic properties by targeting intracellular pathways that regulate collagen disposition. PFD, particularly when delivered via dermal fibroblast-derived exosomes, may further enhance therapeutic effectiveness and promote scarless healing. Two common isolation methods-PEG precipitation and affinity-based techniques-were compared to identify the most efficient approach for obtaining high-purity and relatively homogenous exosomes derived from human dermal fibroblasts. Characterization techniques, including transmission electron microscopy (TEM), atomic force microscopy (AFM), antibody arrays, and enzyme-linked immunosorbent assays (ELISA), confirmed the successful isolation of high-purity exosomes. The affinity-based method demonstrated superior performance, yielding well-dispersed and highly pure exosomes. We optimized the encapsulation and formulation of the antifibrotic compound PFD by exploiting exosomes as a drug delivery platform, employing an active loading method via sonication to enhance encapsulation efficiency (EE%) and loading efficiency (LE%), while carefully controlling the sonication process to preserve exosome integrity. The optimal formulation of PFD-exosomes achieved an EE% of 11.14% ± 1.27% and an LE of 10.01% ± 1.03%, with a particle recovery rate of exosomes at 64.21% ± 8.49% using sonication technique. Then, we investigated how to harness exosomes and PFD-exosomes as innovative strategies for achieving scarless tissue repair in wound healing. Our findings showed that exosomes enhanced fibroblast migration and proliferation, highlighting their potential as a stand-alone cell-free therapy for wound healing. Additionally, this study was ground-breaking in demonstrating that exosomes can improve the efficacy of PFD as a drug carrier, amplifying its anti-fibrotic effects in both in vitro and in vivo models. The in vivo results indicated that PFD-exosomes accelerated wound healing while organizing the extracellular matrix (ECM) by reducing excessive collagen deposition. Overall, PFD-exosomes present an innovative strategy for pre-scarring interventions, offering benefits of enhanced wound healing outcomes while minimizing scarring.

Keywords:  Exosomes; Human Dermal Fibroblasts; Pirfenidone (PFD); Scarless Healing; Wound Healing

DOI:  https://doi.org/10.1007/s13346-026-02108-7
Int J Nanomedicine. 2026 ;21 592579

Engineering Extracellular Vesicles for Tumor Targeted Therapy: Source Optimization, Modification, and Clinical Application.

Jiaxin Sui, HanBin Qin, Zile Zhang, Xiaojing Lv, Xinhua Lin, Zhonglu Liu, Xin Zhao, Xuexia Liu, Hua Zhang.

  Cancer remains a leading cause of global morbidity and mortality, yet conventional therapies, including surgery, radiotherapy, and chemotherapy, are often limited by invasiveness, systemic toxicity, and drug resistance. In this context, extracellular vesicles (EVs) have emerged as a promising cell-free nanotherapeutic platform. As endogenous nanocarriers, EVs enable precise, targeted delivery of diverse bioactive cargoes (eg, nucleic acids, chemotherapeutics, immunomodulators) to tumor tissues, thereby enhancing therapeutic efficacy while minimizing off-target effects, which is the key advantages for their application in tumor targeted therapy. This review systematically summarizes the characteristics of animal-derived and plant-derived EVs and highlights their translational applications in multiple cancers via immune activation, targeted delivery, tumor microenvironment remodeling, and anti-angiogenesis. We further introduce advanced bioengineering strategies for EV modification to optimize cargo loading, targeting specificity, and in vivo stability, particularly frontier innovations such as artificial intelligence-assisted design and microfluidic manufacturing that improve the precision, controllability, and scalability of engineered EVs. Compared to synthetic nanocarriers, EVs exhibit unique advantages, including excellent biocompatibility, low immunogenicity, and superior ability to cross biological barriers. However, the clinical application of EV-based therapies faces notable challenges, including EV heterogeneity, scalability of production, standardization of characterization methods, cargo loading efficiency, and long-term safety concerns. This review emphasizes the transformative potential of engineered EVs in advancing tumor targeted therapy and improving outcomes for patients with refractory or metastatic tumors.

Keywords:  EVs; clinical translation; engineered EVs; extracellular vesicles; tumor microenvironment; tumor targeted therapy

DOI:  https://doi.org/10.2147/IJN.S592579
J Nanobiotechnology. 2026 Apr 11.

Therapeutic potential of ADAR1-regulated macrophage exosomes for improving myocardial damage in septic cardiomyopathy.

Linxiao Wang, Shanshou Liu, Xianqi Wang, Huirong Wu, Xiaojun Zhao, Dan Wu, Qianmei Wang, Peiwen Wang, Yanan Xu, Kuo Shen, Juzheng Yuan, Junjie Li.

   BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is a critical cardiovascular complication characterized by cardiac dysfunction and high mortality. The molecular mechanisms that underlie SICM remain elusive, and effective therapies are limited.
RESULTS: Here, we report a pivotal role for adenosine deaminases acting on RNA-1 (ADAR1) in modulating macrophage polarization and exosome-mediated intercellular communication, which ameliorates myocardial damage in SICM. We determined that ADAR1 overexpression in macrophages promotes an anti-inflammatory M2 phenotype, reduces myocardial inflammation, and inhibits cardiomyocyte apoptosis in a murine model of sepsis. Mechanistically, ADAR1 regulates the level of microRNA-122 (miR-122) in macrophage-derived exosomes. Exosomal miR-122 targets X-linked inhibitor of apoptosis protein (XIAP), modulating cardiomyocyte survival.
CONCLUSIONS: Our study reveals a novel ADAR1-miR-122-XIAP axis in macrophage exosomes that protects against sepsis-induced myocardial injury, offering a potential disease modulation strategy for SICM.

Keywords:  ADAR1; Apoptosis; Cardiomyopathy; Exosomes; MicroRNA; Sepsis

DOI:  https://doi.org/10.1186/s12951-026-04368-4
Theranostics. 2026 ;16(10): 5125-5149

Tumor-targeted Exosomal Delivery of Celastrol for Enhanced Therapeutic Efficacy in NSCLC.

Disha Nagesh Moholkar, Raghuram Kandimalla, Mohd Saeed, Yaseera Arif, Neha Tyagi, Richa Singhal, Al-Hassan Kyakulaga, Amir Saeed, Margaret Wallen, Ramesh Gupta, Farrukh Aqil.

   Rationale: Non-small cell lung cancer (NSCLC) continues to impose a significant global mortality burden, due to limited therapies, drug resistance, and treatment-related toxicity. Exosomes offer promise for the targeted delivery of therapeutic agents.
Methods: Exosomes were isolated from bovine colostrum and characterized for size, polydispersity index, and surface charge. Celastrol (CEL) was loaded onto exosomes (ExoCEL), and Folic Acid (FA)-functionalized exosomes (FA-ExoCEL) and validated using fluorescence quenching and protease sensitivity assay. Anticancer activity was assessed in NSCLC cell lines using colony formation, cell migration and uptake assays. Transcriptomic (RNA-seq) and protein analysis were performed to analyze gene expression changes. Biodistribution, oral uptake and potential toxicity were evaluated in wild-type mice, while oral antitumor efficacy was tested in orthotopic lung tumor models comparing CEL, ExoCEL and FA-ExoCEL. Synergistic activity with paclitaxel was assessed in chemoresistant cells.
Results: Exosomes were isolated, characterized and efficiently loaded with CEL. ExoCEL demonstrated superior antiproliferative effects in NSCLC cell lines and enhanced potency in drug-resistant A549TR cells compared to free CEL. ExoCEL significantly inhibited colony formation and cell migration in a dose-dependent manner. RNA Seq and protein analyses showed that CEL and ExoCEL reversed TGF-β-induced EMT, restored epithelial markers, suppressed mesenchymal, oncogenic and extracellular matrix related markers. In orthotopic lung tumor models, FA-ExoCEL achieved approximately 80-90% tumor inhibition, outperforming both free CEL and ExoCEL. Oral delivery of FA-ExoCEL resulted in efficient gastrointestinal uptake, selective tumor targeting, recovery of exosomal markers in circulation and no observed systemic toxicity. CEL exhibited strong synergy with paclitaxel, with exosomal delivery further enhancing paclitaxel efficacy in resistant cells.
Conclusions: FA-ExoCEL represents a safe, scalable, and effective oral therapeutic strategy for NSCLC. By combining exosome-mediated delivery with folate-targeted tumor accumulation, this platform enhances CEL bioavailability, and improves antitumor efficacy, supporting its translational potential for lung cancer therapy.

Keywords:  Celastrol; Chemoresistance; Epithelial-to-mesenchymal transition (EMT); Exosomes; Lung cancer.; Oral targeted delivery

DOI:  https://doi.org/10.7150/thno.125096
Int J Nanomedicine. 2026 ;21 596983

From Nature to Nanomedicine: Engineered Plant-Derived Nanovesicles for Skin Disease.

Zongshi Yue, Jinping Yin, Yanan Li.

  Plant-derived nanovesicles (PDN), as a novel class of natural nanocarriers, possess excellent biocompatibility and the capacity to load various bioactive components, offering new perspectives for the treatment of skin diseases. However, natural PDN suffer from limited skin penetration and weak targeting ability. By applying engineering strategies such as chemical modification and membrane hybridization, these intrinsic limitations can be effectively overcome, thereby markedly enhancing their therapeutic efficacy against skin diseases. This review provides a systematic summary of the fundamental characteristics and engineering strategies of PDN. Based on the latest research advances, we also outline their therapeutic applications across various skin diseases, including inflammatory, infectious, wounds, aging-related, pigmentary, and tumors. In addition, we propose lesion-adapted administration strategies tailored to different skin diseases. We further highlight the major translational challenges and future opportunities of PDN, providing insight into how these engineered natural nanocarriers may reshape precision and next-generation therapies for skin diseases.

Keywords:  advanced delivery system; biomimetic nanocarriers; dermatological diseases; engineered nanovesicles; exosome-like nanovesicles

DOI:  https://doi.org/10.2147/IJN.S596983
Int J Mol Sci. 2026 Mar 25. pii: 2997. [Epub ahead of print]27(7):

miR-4516-Loaded Engineered Milk Extracellular Vesicles Attenuate Indoxyl Sulfate-Induced Mitochondrial Dysfunction and Improve Renal Function in a CKD Mouse Model.

Jeongkun Lee, Jun Young Yoon, Jae Young Lee, Sang Hun Lee.

  Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular-endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD.

Keywords:  chronic kidney disease; indoxyl sulfate; miR-4516; milk-derived extracellular vesicles; mitochondrial dysfunction

DOI:  https://doi.org/10.3390/ijms27072997
Int Immunopharmacol. 2026 Apr 16. pii: S1567-5769(26)00503-5. [Epub ahead of print]179 116658

Engineered mesenchymal stem cell-derived extracellular vesicles attenuate acute glaucoma-induced neuroinflammation by reprogramming microglial polarization.

Aixiang Luo, Haiyang Yu, Tianqi Duan, Min Li, Ruping Zheng, Shuangyan He, Jufang Huang.

  Retinal microglia-mediated neuroinflammation is a critical driver of pathological damage in glaucoma, leading to irreversible loss of retinal ganglion cells (RGCs). Current treatments remain limited in effectively targeting and modulating this neuroinflammatory component within the retinal microenvironment. To address this, we engineered cRGD peptide-functionalized mesenchymal stem cell (MSC)-derived extracellular vesicles (cRGD-EVs) capable of actively targeting activated microglia for the localized delivery of anti-inflammatory miRNAs. After intravitreal administration, cRGD-EVs demonstrated enhanced accumulation in the retina and specific uptake by activated microglia in a rat model of retinal ischemia/reperfusion (RIR) injury. Both in vitro co-culture models and in vivo analyses confirmed the targeting efficacy and phenotypic reprogramming of microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2) state. Intravitreal injection of cRGD-EVs loaded with key miRNAs (let-7c-5p, miR-21a-5p, and miR-146a-5p) significantly suppressed NF-κB pathway activation and reduced the expression of downstream pro-inflammatory cytokines. Treated animals exhibited notable preservation of retinal structure, increased RGC survival, and significant recovery of visual function, as measured by electroretinography. Furthermore, in acute ocular hypertension model, cRGD-EV treatment attenuated glaucomatous neurodegeneration and improved overall retinal homeostasis. These findings highlight cRGD-EVs as a promising targeted biologic delivery system for treating neuroinflammatory components of glaucoma and potentially other retinal diseases characterized by microglial activation.

Keywords:  Extracellular vesicles; Glaucoma; Mesenchymal stem cells; Microglia; Retinal ganglion cell

DOI:  https://doi.org/10.1016/j.intimp.2026.116658
Extracell Vesicles Circ Nucl Acids. 2026 ;7(1): 16-19

Selenized neural stem cell exosomes for CNS trauma repair.

Lina Zhu, Kailu Guo, Xi Liu, Yanlin Feng, Cuiping Zhang.

  A recent study on Cell Reports Medicine by Wang et al. introduces a hybrid exosome platform - selenized neural stem cell-derived exosomes (SeNExo) - that couples the biological functionality of neural stem cell exosomes with the antioxidant power of ultrasmall nanoselenium. SeNExo crosses the blood-brain barrier via apolipoprotein E (APOE)-lipoprotein receptor-associated protein-1 (LRP1) interaction, scavenges reactive oxygen species, and restores glial-neuron homeostasis. It demonstrates potent therapeutic efficacy in both traumatic brain injury and spinal cord injury mouse models. This work highlights a promising direction for engineering multifunctional, cell-free nanotherapeutics for central nervous system repair.

Keywords:  Exosomes; blood-brain barrier; neural stem cells; selenium; spinal cord injury; traumatic brain injury

DOI:  https://doi.org/10.20517/evcna.2025.156