bims-engexo 2026-08-23 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–08–23
eight papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Surface-engineered GE11-functionalized exosomes for EGFR-targeted peonidin delivery and suppression of SNAI1-mediated epithelial-mesenchymal transition in glioma.
Emerging bacterial membrane vesicles from microbial messengers to therapeutic nanocarriers.
Exosomes as next-generation drug carriers: Transforming cancer therapy.
Engineered exosome-lymphotropic mRNA vaccine encoding series-connected antigens elicits potent antitumor immunity in pancreatic cancer.
Astragaloside IV and rapamycin co-loaded bone marrow mesenchymal stem cell-derived exosome nanocarriers for targeted modulation of the PI3K/Akt/mTOR pathway in hepatocellular carcinoma.
A multifunctional DECM/PLMA hydrogel incorporated with engineered PRP-derived exosomes enabling PHD2 silencing for skin wound repair.
Engineered Exosome-Mediated FIH-1 Delivery for Targeted Therapy of Hyperuricemic Nephropathy by Inhibiting NF-κB/NLRP3 Inflammasome Signaling and Restoring Autophagic Homeostasis.
Milk-derived extracellular vesicles: nutritional significance, nano-delivery potential, and emerging therapeutic applications - an updated review.

Colloids Surf B Biointerfaces. 2026 Aug 19. pii: S0927-7765(26)00669-7. [Epub ahead of print]268(Pt 2): 116081

Surface-engineered GE11-functionalized exosomes for EGFR-targeted peonidin delivery and suppression of SNAI1-mediated epithelial-mesenchymal transition in glioma.

Yang Bai, Yuexiang Jin, Yining Jiang, Bo Liu, Chun Chen.

  Glioblastoma is a highly aggressive and invasive brain tumor with poor prognosis, largely due to its rapid progression, epithelial-mesenchymal transition (EMT)-mediated invasiveness, and resistance to conventional therapies. Herein, the surface-engineered exosomal nanoplatform for targeted glioma therapy is functionalized glioblastoma-derived exosomes with the epidermal growth factor receptor (EGFR)-targeting GE11 peptide and loading them with peonidin (PN), a naturally occurring anthocyanin with anticancer potential. The engineered Exo-GE11/PN nanoparticles exhibited favorable physicochemical characteristics, including nanoscale size distribution, high encapsulation efficiency, colloidal stability, and preserved exosome morphology. GE11 functionalization significantly enhanced cellular uptake in EGFR-overexpressing glioma cells, facilitating efficient intracellular delivery of PN. In vitro studies demonstrated that Exo-GE11/PN effectively suppressed glioma cell proliferation, migration, and invasion while promoting apoptotic cell death. Mechanistic investigations revealed that the formulation attenuated EMT through downregulation of SNAI1 and modulation of the PI3K/Akt/NF-κB signaling pathway, accompanied by restoration of epithelial markers and suppression of mesenchymal markers. Furthermore, Exo-GE11/PN significantly reduced tumor growth and improved survival in glioma-bearing mice without inducing clear systemic toxicity, confirming its biocompatibility and therapeutic efficacy. Collectively, these findings highlight the importance of exosome surface engineering for targeted drug delivery and demonstrate that GE11-functionalized exosomes serve as an effective biointerface-mediated carrier for peonidin. This biomacromolecular nanoplatform offers a promising strategy for EGFR-targeted glioblastoma therapy through the suppression of EMT-associated oncogenic signaling pathways.

Keywords:  EGFR-targeted delivery; GE11 peptide; Glioblastoma; Peonidin; Surface-engineered exosomes

DOI:  https://doi.org/10.1016/j.colsurfb.2026.116081
J Control Release. 2026 Aug 16. pii: S0168-3659(26)00654-1. [Epub ahead of print]398 115250

Emerging bacterial membrane vesicles from microbial messengers to therapeutic nanocarriers.

Giulia Elayna Stewart, Yitong Guo, Shijie Cao.

  Bacterial membrane vesicles (BMVs) are nanoscale vesicles that are naturally released by bacteria into the extracellular environment. By retaining the bacterium's membrane and luminal cargo, BMVs represent natural nanocarriers and long-distance messengers capable of influencing human health and disease progression. Depending on the bacterial species of origin, BMVs present important transport roles by carrying diverse native molecular cargo, protecting luminal cargo from degradation, promoting intracellular delivery and cytosolic release, crossing biological barriers, and mediating interactions with host cells. Recently, engineering strategies have emerged to harness these natural nanocarriers for the improved delivery of a wide range of therapeutic cargos, including proteins, antigens, nucleic acids, oncolytic viruses, polymers, and nanoparticles. These engineering strategies include genetic engineering, encapsulation, surface modification, and detoxification methods. Together, these strategies provide features including superior loading efficiency, targeted delivery, controlled release, longer circulation time, and multi-composite delivery approaches. This review discusses BMVs as versatile, multi-functional, and bio-active delivery vehicles along with current preparation methods, delivery routes, engineering strategies, highlighting unique features and challenges for translation.

Keywords:  Bacterial membrane vesicles; Cytoplasmic membrane vesicles; Drug delivery systems; Engineering strategies; Microbiome; Outer membrane vesicles

DOI:  https://doi.org/10.1016/j.jconrel.2026.115250
J Control Release. 2026 Aug 15. pii: S0168-3659(26)00669-3. [Epub ahead of print]398 115265

Exosomes as next-generation drug carriers: Transforming cancer therapy.

Yaseera Arif, Disha Nagesh Moholkar, Raghuram Kandimalla, Farrukh Aqil, Ramesh C Gupta.

  Cancer remains a major global health challenge, with its growing incidence highlighting the critical need for effective and accessible treatments. Current therapeutic approaches, including surgery, chemotherapy, radiation therapy, hormone therapy, and immuno-therapy, are often limited by toxicity, poor targeting, and suboptimal efficacy. These challenges have driven the development of nanotechnology-based strategies aimed at improving tumor selectivity and therapeutic outcomes. Among the most promising are extracellular vesicles, particularly exosomes (30-150 nm), which have garnered significant attention as natural nanocarriers due to their inherent role in intercellular communication and their capacity to encapsulate proteins, nucleic acids, and lipids. Exosomes can be obtained from a wide range of sources, including biological fluids, cell cultures, and unconventional origins such as plants and microorganisms. Of particular interest, milk- and colostrum-derived exosomes, particularly those of bovine origin, have emerged as a promising delivery platform owing to their scalability, biocompatibility, cost-effectiveness and suitability for oral administration. These vesicles possess immunomodulatory properties, demonstrate stability under gastrointestinal conditions, and are readily internalized by intestinal epithelial cells. Furthermore, surface engineering with targeting ligands such as folic acid can enhance tumor specific delivery by exploiting receptor overexpression while minimizing systemic toxicity. This review critically examines exosome sources, isolation and characterization methodologies, cargo-loading strategies, biodistribution, pharmacokinetics, and engineering approaches together with their applications in delivering small-molecule drugs and nucleic acid-based therapeutics to overcome multidrug resistance in cancer. In addition, current challenges related to exosome heterogeneity, manufacturing, quality control, clinical translation, and regulatory considerations are discussed, together with future perspectives for the development of exosome-based therapeutics.

Keywords:  Cancer therapy; Drug delivery; Exosomes; Extracellular vesicles; Multidrug resistance; Nucleic acid therapeutics

DOI:  https://doi.org/10.1016/j.jconrel.2026.115265
Int J Pharm. 2026 Aug 21. pii: S0378-5173(26)00775-1. [Epub ahead of print] 127327

Engineered exosome-lymphotropic mRNA vaccine encoding series-connected antigens elicits potent antitumor immunity in pancreatic cancer.

Yijia Li, Jiaying Jin, Kemeng Chen, Siyu Yao, Long Yang, Yuxing Lin, Wenbing Dai, Hua Zhang, Bing He, Lei Miao, Qiang Zhang, Xueqing Wang.

  Pancreatic ductal adenocarcinoma (PDAC) is driven by KRAS mutations in over 90% of cases yet remains refractory to most therapies due to poor antigen delivery and a suppressive tumor microenvironment. To address these challenges, we developed an exosome‑augmented, epitope‑focused mRNA nanovaccine. First, we engineered a series-connected (SC) mRNA that condenses five immunodominant KRAS‑mutant epitopes (G12D, G12V, G12R and two other sequences) into a single open reading frame. This design minimizes non‑productive sequence and enhances antigen presentation compared to a conventional parallel-connected (PC) mixture of full‑length transcripts. Second, we cloaked β‑sitosterol LNPs with mature dendritic‑cell-derived exosomes (LNP@exo), endowing the particles with lymph‑node tropism and intrinsic adjuvanticity. The resulting mKRAS SC-LNP@exo triggered potent dendritic cell activation and Th1 cytokine release in vitro, rapidly accumulated in lymph nodes, and drove superior CD8⁺ T cell infiltration in a Pan02 tumor model. Remarkably, one‑third of mKRAS SC-LNP@exo treated mice achieved complete tumor regression without off‑target toxicity. These findings demonstrate that combining epitope‑condensed mRNA with exosome‑cloaked LNP delivery can convert "cold" KRAS‑mutant PDAC into an immunologically responsive tumor and provide a broadly applicable strategy for next‑generation mRNA cancer vaccines.

Keywords:  KRAS; Lipid nanoparticle; Pancreatic ductal adenocarcinoma; Series‑connected epitopes; Tumor immunotherapy; mRNA vaccine

DOI:  https://doi.org/10.1016/j.ijpharm.2026.127327
Nanomedicine (Lond). 2026 Aug 20. 1-23

Astragaloside IV and rapamycin co-loaded bone marrow mesenchymal stem cell-derived exosome nanocarriers for targeted modulation of the PI3K/Akt/mTOR pathway in hepatocellular carcinoma.

Jing Zhang, Dongdong Gao.

   BACKGROUND: Hepatocellular carcinoma (HCC) remains a highly aggressive malignancy with poor therapeutic outcomes due to drug resistance, systemic toxicity, and limited tumor-targeted drug delivery. This study aimed to develop dual-drug-loaded exosome nanocarrier encapsulating rapamycin (RAP) and Astragaloside IV (AST-IV) (RAP@AST-IV/EXO NC) to inhibit PI3K/Akt/mTOR signaling and enhance mitochondrial apoptosis in HCC.
METHODS: Bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exos) were isolated and used for co-delivery of RAP and AST-IV via sonication-assisted loading. Physicochemical properties, drug loading, and release behavior were evaluated. In vitro efficacy was assessed through cell viability, apoptosis, ROS generation, mitochondrial membrane potential, migration, and Western blot assays. In vivo therapeutic efficacy and safety were evaluated in male BALB/c mice bearing HepG2 xenografts.
RESULTS: RAP@AST-IV/EXO NC showed favorable physicochemical characteristics, sustained drug release, enhanced apoptosis, increased ROS generation, mitochondrial membrane disruption, and inhibition of cancer cell migration. The RAP@AST-IV/EXO NC significantly reduced cell viability and suppressed phosphorylated PI3K, Akt, and mTOR expression while activating mitochondrial apoptotic markers. In vivo, RAP@AST-IV/EXO NC markedly inhibited tumor growth without evident systemic toxicity.
CONCLUSION: RAP@AST-IV/EXO NC represent a promising biocompatible strategy for targeted HCC therapy through combined PI3K/Akt/mTOR inhibition and mitochondrial apoptosis induction.

Keywords:  Astragaloside IV; Hepatocellular carcinoma; apoptosis; exosomes; rapamycin

DOI:  https://doi.org/10.1080/17435889.2026.2698784
Bioact Mater. 2027 Jan;67 306-326

A multifunctional DECM/PLMA hydrogel incorporated with engineered PRP-derived exosomes enabling PHD2 silencing for skin wound repair.

Xiangyu Du, Danmei Li, Hongpu He, Guangxun Yuan, Pengju Liu, Binbin Ma, Chengjie Yuan, Yijun Zhang, Jian Xu.

  Skin defect repair remains a formidable clinical challenge, characterized by persistent infection risk, compromised angiogenesis, and dysregulated inflammatory responses. Existing hydrogel-based wound dressings fail to simultaneously address structural integrity, antimicrobial efficacy, and spatiotemporal coordination of tissue regeneration. Here, we report the development of a multifunctional bioactive hydrogel system fabricated by integrating decellularized tendon extracellular matrix (DECM) with Poly-L-lysine Methacryloyl (PLMA), and further functionalized with engineered platelet-rich plasma exosomes (PRP-Exos) loaded with siRNA targeting prolyl hydroxylase domain protein 2 (PHD2) via electroporation. The inherent cationic nature of PLMA confers robust, broad-spectrum antibacterial activity, while the sustained release of siRNA-PHD2-laden PRP-Exos achieves efficient PHD2 silencing, thereby stabilizing hypoxia-inducible factor-1α (HIF-1α) and potentiating downstream pro-angiogenic signaling. Concurrently, bioactive cues released from the DECM-based matrix promote fibroblast-to-myofibroblast differentiation and type I collagen biosynthesis, fostering a regeneration-permissive microenvironment. In both normal and diabetic murine full-thickness skin defect models, DEPL@E-SI significantly accelerated wound closure by promoting angiogenesis, inflammation resolution, and extracellular matrix remodeling. These findings establish DEPL@E-SI as a promising therapeutic platform with translational potential for skin tissue engineering and clinical wound management.

Keywords:  Decellularized tendon extracellular matrix; Hydrogel; PHD2 silencing; Platelet-rich plasma exosomes; Poly-L-lysine methacryloyl; Skin defect repair

DOI:  https://doi.org/10.1016/j.bioactmat.2026.08.004
Adv Healthc Mater. 2026 Aug 16. e71602

Engineered Exosome-Mediated FIH-1 Delivery for Targeted Therapy of Hyperuricemic Nephropathy by Inhibiting NF-κB/NLRP3 Inflammasome Signaling and Restoring Autophagic Homeostasis.

Ting Xiao, Yu Liu, Zhe He, Ailing Yang, Jing Li, Li Zhou, Qingxiang Yang, Dunquan Xu, Lijia Yuan, Ming Chen, Sha Yang.

  Renal tubular epithelial fibrosis is a key pathological process in the progression of hyperuricemia (HUA), and hyperuricemic nephropathy (HN). Targeted inhibition of renal tubular epithelial cell (RTEC) fibrosis represents a promising therapeutic strategy for HN. Extracellular vesicles derived from induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) were engineered as nanostructured delivery vehicles incorporating two functional modules: a kidney-targeting module and a functional protein module. The targeting module was constructed by anchoring cholesterol-modified RTEC-specific peptides onto the extracellular vesicle membrane to enhance selective accumulation in RTECs. The functional protein module consisted of extracellular vesicles enriched with factor inhibiting hypoxia-inducible factor 1 (FIH-1). Functional analyses demonstrated that FIH-1 delivery effectively suppressed uric acid (UA)-induced fibrotic responses by inhibiting activation of the NF-κB/NLRP3 inflammasome signaling pathway and restoring dysregulated autophagy. These coordinated regulatory effects resulted in significant downregulation of renal tubular epithelial injury. The targeting capability and therapeutic efficacy of the engineered extracellular vesicle system were further validated in both in vitro and in vivo models of HUA-associated renal injury. Collectively, these findings establish a targeted exosome-based nanotherapeutic strategy for the precision treatment of HN and provide a conceptual framework for the development of next-generation engineered extracellular vesicle platforms in regenerative medicine.

Keywords:  autophagy; downregulation and upregulation; exosome; extracellular vesicle; inflammasome; mesenchymal stem cell; microvesicles; regenerative medicine; signal transduction; targeted therapy

DOI:  https://doi.org/10.1002/adhm.71602
Food Sci Anim Resour. 2026 Aug 21. pii: 96. [Epub ahead of print]46(1):

Milk-derived extracellular vesicles: nutritional significance, nano-delivery potential, and emerging therapeutic applications - an updated review.

Suqin Wang, Aftab Shaukat, Mohammed Al-Rasheed, Abdul Malik Tareen, Muhammad Asif Arain, Congqiang Luo.

  Milk-derived extracellular-vesicles (mEVs) have emerged as a promising natural nanocarriers for nutraceutical and therapeutic applications, owing to their rich cargo of bioactive proteins, lipids, microRNAs, and metabolites, coupled with their inherent biocompatibility and stability. Their unique ability to withstand gastrointestinal degradation and cross biological barriers, such as blood-brain-barrier, while eliciting minimal immunogenicity provide a distinct advantage over synthetic delivery systems. Furthermore, mEVs can also be engineered or enriched with functional molecules, enabling the targeted delivery of nutraceuticals, chemotherapeutic agents, anti-inflammatory compounds, and gene regulators. Growing evidence demonstrates their capacity to modulate immune functions, support gut integrity, mitigate oxidative stress, regulate inflammatory processes, and influence systemic metabolic and neurophysiological pathways. However, their translational potential, key challenges, including scale isolation, optimize cargo loading, and comprehensive functional characterization, still limit their broader application. This review summarizes the biological properties, isolation strategies, and therapeutic prospects of mEVs, emphasizing their dual role as nutrition component and precision delivery platforms. Additionally, this review enhances our understanding regarding the beneficial application of milk-EVs as a natural, nontoxic and efficient nutraceutical carrier for next-generation nutraceutical and biomedical innovations.

Keywords:  Extracellular vesicles; Health benefits; Nanocarrier for precision medicine

DOI:  https://doi.org/10.1007/s44463-026-00104-6