bims-engexo 2026-01-25 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–01–25
ten papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineering exosomes for cancer therapy - Modification technologies and subcellular targeting strategies: A review.
Coconut milk exosomal formulation of curcumin analog targets head and neck cancer progression through alterations in the HABP1 signaling mechanism.
Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer.
An Engineered Nanovesicles-Based Lysosome-Targeting Protein Degradation Platform (NV-TACs) for Cancer Immunotherapy.
MiR-146a-armed exosomes reverse immunosuppressive networks in NSCLC by dual-targeting of MYD88/STAT3 and PD-L1 axes.
Co-delivery of panobinostat and siSTAT3 using engineered M1 exosomes to establish a one-two punch therapeutic strategy for glioblastoma recurrence.
Oral Delivery of R-spondin1-Loaded Small Extracellular Vesicles Activates WNT Signalling Pathway to Accelerate Intestinal Injury Repair and Reverse Ageing.
miR-19b-3p engineered adipose-derived stem cell exosomes attenuate acute liver failure via promoting tissue repair and microenvironment remodeling.
Nano-delivery system of milk-derived exosomes loaded with Forsythiaside A: Studies on bovine mammary epithelial cells and mastitis induced mice.
Homologous tumor cell exosome-based drug delivery system co-delivering temozolomide and resveratrol for orthotopic glioblastoma therapy.

Int J Pharm X. 2026 Jun;11 100473

Engineering exosomes for cancer therapy - Modification technologies and subcellular targeting strategies: A review.

Fengbo Liu, Chengxing Xia, Hang Yu, Xiaofang Yang, Liping Ge, Chunwei Ye.

  Exosomes are secreted lipid bilayer vesicles of 30-150 nm in diameter. Their low immunogenicity, excellent biocompatibility, and inherent targeting capability make them a promising drug delivery vehicle for cancer therapeutics. However, the use of natural exosomes is still challenging for therapeutic applications, including limited targeting precision and drug-loading efficiency, necessitating engineered modification strategies to optimize their performance. To further enhance exosome targeting capacity, recent studies have explored precision delivery strategies targeting subcellular structures such as lysosomes, nuclei, mitochondria, and the endoplasmic reticulum, thereby improving exosome therapeutic potential. This review systematically summarizes the core advantages of exosomes as drug carriers, elaborates on their engineering modification methods, and highlights recent advances in strategies to improve exosomes targeting of subcellular structures to enhance antitumor efficacy. The review aims to provide a theoretical foundation and technical guidance for developing exosome-based precision therapies for cancer.

Keywords:  Cancer; Exosome; Modification; Subcellular targeting; Therapy

DOI:  https://doi.org/10.1016/j.ijpx.2025.100473
Cancer Treat Res Commun. 2026 Jan 09. pii: S2468-2942(26)00011-0. [Epub ahead of print]46 101102

Coconut milk exosomal formulation of curcumin analog targets head and neck cancer progression through alterations in the HABP1 signaling mechanism.

Kaumudi Pande, Bettadaiah B K, Anbarasu Kannan.

   BACKGROUND: Head and neck cancer (HNC) is a malignancy characterized by uncontrolled cell growth with increasing incidence rates and heterogeneity. Hyaluronan binding protein 1 (HABP1) is a glycoprotein that acts as a cell surface marker, influencing the immune tumor environment, and is overexpressed in various epithelial tumors. The role of HABP1 in HNC remains to be investigated. Exosome therapy has emerged as a promising treatment that delivers anticancer compounds directly to tumor sites. Coconut milk is considered a valuable therapeutic agent against cancer. Curcumin Analog Isoleucine (CAI) exhibits better solubility, improved antioxidant properties, and greater antimutagenic effects than curcumin. In the study, we emphasized on exosomal delivery of CAI to affect HABP1 signaling for effective cancer therapy.
METHODS: The study focused on the isolation and characterization of tender coconut milk-derived exosomes. Exosomal formulation was developed by loading tender coconut milk-derived exosomes with CAI (TC EXO+CAI) through the sonication method. Bioaccessibility assessment was executed for the TC EXO+CAI along with the MTT assay, morphology, nucleus shape, colony formation, AO-EtBr assays, western blot, and gene expression analysis.
RESULTS: The bioaccessibility of TC EXO+CAI was greater than that of CAI or curcumin. TC EXO+CAI was cytotoxic to HNC cells at a lower IC50 value, indicating effective CAI delivery by exosomes. It causes cell shrinkage, nuclear condensation, fewer colonies, and an increased number of apoptotic HNC cells. It reduced the expression levels of HABP1 and associated molecules in HNC cells. The uptake of TC EXO+CAI by HNC cells increases the expression of p53 and caspases, which effectively activates the apoptosis mechanism.
CONCLUSION: TC EXO+CAI exhibits target-specific delivery, which affects tumor cell physiology by reducing HABP1 levels and prompting apoptosis in HNC cells.

Keywords:  Anticancer; Bioaccessibility; Curcumin analog isoleucine; Exosomes

DOI:  https://doi.org/10.1016/j.ctarc.2026.101102
Adv Sci (Weinh). 2026 Jan 20. e13369

Dual Targeting of Mutant p53 and SNRPD2 via Engineered Exosomes Modulates Alternative Splicing to Suppress Ovarian Cancer.

Wei Zhao, Qian Hao, Yu Gan, Jing Tong, Xiaodan Chen, Shuran Tan, Ruiwen Ruan, Yingdan Huang, Mingming Cao, Jun Deng, Tao Han, Getao Shi, Bo Gao, Yu Zhang, Xiang Zhou.

  Mutation of the tumor suppressor gene TP53 promotes ovarian cancer progression and therapeutic resistance. Whether mutant p53 (mtp53) regulates alternative splicing and how this regulation can be exploited for cancer therapy remain unclear. Here, small nuclear ribonucleoprotein D2 polypeptide (SNRPD2) as a binding partner of mtp53 is identified. SNRPD2 is highly expressed in ovarian cancer and associated with an unfavorable prognosis. The overexpression of SNRPD2 promotes, whereas its depletion inhibits, the growth and migration of ovarian cancer cells. Mechanistically, mtp53 cooperates with SNRPD2 to facilitate the assembly of the Sm/SMN protein complex, an essential component of the spliceosome, modulating alternative splicing of pre-mRNAs. Specifically, the co-depletion of mtp53 and SNRPD2 reduces the level of OTUD3 oncogenic transcripts while increasing its tumor suppressor counterparts through an exon-skipping event. Moreover, therapeutic engineered exosomes are developed with their surfaces decorated with iRGD and their interiors loaded with siRNAs targeting mtp53 and SNRPD2. These exosomes effectively suppress the growth of ovarian cancer cells and enhance their sensitivity to chemotherapy in vivo. Collectively, this study uncovers that mtp53 and SNRPD2 cooperatively regulate alternative splicing to drive ovarian cancer progression, and co-targeting these two molecules via engineered exosomes represents a potential therapeutic strategy for ovarian cancer.

Keywords:  SNRPD2; alternative splicing; engineered exosomes; p53; targeted therapy

DOI:  https://doi.org/10.1002/advs.202513369
J Am Chem Soc. 2026 Jan 21.

An Engineered Nanovesicles-Based Lysosome-Targeting Protein Degradation Platform (NV-TACs) for Cancer Immunotherapy.

Youmei Xiao, Xiuman Zhou, Xiaoshuang Niu, Xiaoyun Ye, Danhong Chen, Qingyu Dong, Zhuoying He, Xin Yang, Mengfan Wang, Wenxuan Zeng, Ye Su, Feiyu Luo, Juan Liu, Yanfeng Gao.

Lysosome-Targeting Chimeras (LYTAC) technology offers a revolutionary approach for specifically degrading extracellular and membrane proteins. However, current LYTAC platforms face multiple technical challenges, including ligand screening, linker optimization, and the need to balance the characteristics between the protein of interest (POI) and lysosome-targeting receptor (LTR). To overcome these challenges, we engineered NV-TACs (Nanovesicle-based TArgeting Chimeras)─a linker-free LYTAC platform that integrates native nanovesicles displaying the endogenous ligands of POI and LTRs as bioinspired membrane protein degradation modules. As a proof-of-concept, PD-1 (as the binder of PD-L1) and transferrin (as the binder of transferrin receptor, TFRC) were engineered into biocompatible fibroblast-derived nanovesicles. This platform demonstrates significant scalability, allowing flexible module integration and functional assembly. NV-TACs efficiently degrade PD-L1 on tumor and immune cells through the TFRC-mediated specific lysosomal endocytosis pathway, and it has been expanded to the degradation of other membrane proteins. Notably, by incorporation of a therapeutic payload (ML210), NV-TACs simultaneously exhibited targeted protein degradation and ML210-mediated ferroptosis through payload delivery capacity. Both in anti-PD-1-responsive and -resistant tumor models, NV-TACs demonstrated significant therapeutic efficacy without obvious systemic toxicity. The platform of NV-TACs paves new avenues for developing linker-free, modular, and bioinspired targeted protein degradation platforms.

DOI: https://doi.org/10.1021/jacs.5c17801
Int Immunopharmacol. 2026 Jan 21. pii: S1567-5769(26)00016-0. [Epub ahead of print]172 116173

MiR-146a-armed exosomes reverse immunosuppressive networks in NSCLC by dual-targeting of MYD88/STAT3 and PD-L1 axes.

Mina Alimohammadi, Safa Tahmasebi, Davar Amani, Babak Salimi, Mahsa Hajivalili, Ian M Adcock, Esmaeil Mortaz.

   BACKGROUND: MiR-146a has been found to be a tumor suppressor and is downregulated in NSCLC cells. This study investigated the effects of delivering miR-146a via tumor-derived exosomes (TEX-MiR-146a) on the behavior of malignant cells and immunological modulation in NSCLC models.
METHODS: miR-146a expression was evaluated in A-549 and normal MRC-5 lung epithelial cells. Exosomes were isolated from A-549 cells, loaded with a miR-146a mimic, and characterized for size, morphology, surface markers, and loading efficiency. In vitro, the functional effects of TEXmiR-146a were compared to controls using tests for cell survival, apoptosis, migration, invasion, wound healing, colony formation, and gene expression. Co-culture immunological assays, including T cell subset and cytokine profiling, were also performed using patient-derived peripheral blood mononuclear cells (PBMCs).
RESULTS: TEXmiR-146a efficiently loaded miR-146a into cells (60.1 % ± 4.0 efficiency, P < 0.0001). Treatment with TEXmiR-146a (25 μg/ml) significantly reduced the viability of A-549 cells by ∼51 % after 48 h (P < 0.0001). Cell migration and invasion were inhibited by >50 %, with migrating cells reduced to 116.7 ± 7.09 (P < 0.001) and invading cells to 171.7 ± 6.028 (P < 0.001), respectively, compared to controls. Pro-apoptotic genes Bax/Bcl-2 (P = 0.0002) and Caspase-3 were upregulated (P = 0.0003), while metastatic and immunoregulatory genes VEGF-A, MMP-9, STAT3, MYD88, and PD-L1 were downregulated (all P < 0.05). In patient PBMCs, TEXmiR-146a increased the frequency of cytotoxic CD8+ T cells (24.75 ± 1.23 % versus 20.15 ± 1.26 %, P < 0.0001) and decreased Treg cells (2.01 ± 1.22 % versus 4.04 ± 1.72 %, P = 0.015) compared to the TEX group, alongside a significant reduction in TGF-β (P = 0.01).
CONCLUSION: Exosomal delivery of miR-146a effectively restores tumor suppressor functions and reverses immunosuppressive networks in NSCLC by dual-targeting key oncogenic and immunomodulatory axes, presenting a potent cell-free immunotherapeutic strategy.

Keywords:  Anti-tumor immunity; Apoptosis; Invasion; MiR-146a; Non-small cell lung cancer; Tumor exosome (TEX)

DOI:  https://doi.org/10.1016/j.intimp.2026.116173
Mater Today Bio. 2026 Feb;36 102680

Co-delivery of panobinostat and siSTAT3 using engineered M1 exosomes to establish a one-two punch therapeutic strategy for glioblastoma recurrence.

Xuemeng Liu, Yaotian Hu, Yan Zhang, Chang Liu, Jingwen Wu, Ruiqi Zhao, Zhiyi Xue, Wenjing Zhou, Xiaofei Liu, Hrvoje Miletic, Yongli Gao, Chen Qiu, Jian Wang.

  Effectively treating recurrent glioblastoma (GB) remains a significant challenge in the clinic. Considering the multifactorial nature of GB progression, a comprehensive therapeutic strategy that directly targets both the tumor cells and its microenvironment is crucial. In this study, we developed an approach using exosomes derived from genetically modified M1 macrophages that encapsulate panobinostat and siSTAT3 to treat recurrent GB. We demonstrate that this innovative system has an innate ability to actively home to tumor cells, leveraging the inflammation-targeting capabilities of M1 macrophage-derived exosomes. These exosomes are pivotal in shifting the balance from M2 macrophages to the more favorable M1 phenotype within the tumor microenvironment. By loading the exosomes with panobinostat, a compound that faces challenges crossing the blood-brain barrier, it can efficiently access and act upon the tumor. Moreover, with the co-delivery of siSTAT3, the exosomes display various functionalities, such as inhibiting GB proliferation and invasion, preventing astrocyte reactivity, and reducing M2 macrophage infiltration. This "one-two punch" approach offers a powerful combined anticancer effect through simultaneously targeting tumor cells and reshaping the tumor microenvironment, which holds considerable promise in curbing GB recurrence and provides hope for more effective future treatments.

Keywords:  Exosome; Glioblastoma; M1 macrophage; Panobinostat; Tumor microenvironment; siSTAT3

DOI:  https://doi.org/10.1016/j.mtbio.2025.102680
J Extracell Vesicles. 2026 Jan;15(1): e70226

Oral Delivery of R-spondin1-Loaded Small Extracellular Vesicles Activates WNT Signalling Pathway to Accelerate Intestinal Injury Repair and Reverse Ageing.

Lingyan Yang, Xu Wang, Xiyang Wei, Pei Yu, Yue Liu, Shixiang Wang, Yuefang Lin, Yue Yang, Ting Jiang, Zhiping Qiao, Jiaxiang Zhang, Shicheng Yu, Ye-Guang Chen, Yun-Shen Chan.

  The intestine plays a crucial role in regulating metabolism and immunity, with functional decline occurring during injury and ageing. Stimulating the neogenesis of intestinal stem cells (ISCs) by activating the WNT/β-catenin signalling pathway represents a promising approach for intestinal tissue regeneration and injury repair. However, effective oral delivery of functional WNT signalling agonists to the gut remains challenging. Herein, we report a potent WNT/β-catenin signalling-inducing small extracellular vesicles (sEV) that can be administered orally and present remarkable therapeutic efficacy. We demonstrate that active R-spondin1 (RSPO1) protein can be loaded onto the surface of sEV via heparan sulfate proteoglycans. Notably, sEV-delivered RSPO1 (evRSPO1) effectively induces WNT/β-catenin signalling-inducing activity, enhances ISCs proliferation, and supports intestinal organoid growth in vitro. Importantly, oral administration of evRSPO1 activates the WNT/β-catenin signalling pathway in the cryptic stem cell niche, thereby accelerating tissue repair and regeneration in a radiation-induced intestinal injury model. Furthermore, evRSPO1 treatment induces ISCs proliferation and reverses the intestinal senescence phenotype in aged mice. Collectively, this study establishes evRSPO1 as a potential first-in-class, orally deliverable therapeutic that overcomes biological barriers to activate ISCs, enabling efficient intestinal tissue repair and rejuvenation.

Keywords:  R‐spondin1; WNT signalling; ageing reversal; extracellular vesicles; intestinal regeneration

DOI:  https://doi.org/10.1002/jev2.70226
Mater Today Bio. 2026 Feb;36 102697

miR-19b-3p engineered adipose-derived stem cell exosomes attenuate acute liver failure via promoting tissue repair and microenvironment remodeling.

Baitong Wu, Jiuxing Feng, Xi Wang, Jingyi Guo, Lanyue Sheng, Jian Wang, Jiaqi Xu, Jie Zhou, Guangming Wang, Yi Wen, Jiaxin Liu, Shu Zhao, Danjing Yang, Yinpeng Jin, Qingchun Fu, Jun Xu.

  Acute liver failure (ALF) is a life-threatening clinical syndrome, characterized by rapid hepatocyte injury and deteriorating hepatic microenvironment. To date, there is still no effective clinical treatment for ALF. Adipose-derived stem cells (ADSCs) have been proven to be an ideal seed-cell in tissue engineering and regenerative medicine through ADSCs-derived exosomes (ADSC-EXO) by paracrine effect. Herein, we presented an ADSC-EXO based therapeutic strategy that could facilitate microenvironment reconstruction and tissue repairing simultaneously in ALF. We demonstrated that miR-19b-3p exhibited remarkable anti-inflammation and anti-oxidation effect. Functionalized exosomes miR-19-EXO administration elevated survival rates from 25 % to 75 %, concurrently reversing liver function, promoting histoarchitectural integrity, and ameliorating inflammatory infiltration in vivo. Mechanistically, miR-19b-3p directly targeted p47phox (a NADPH oxidase subunit) and impede hepatic oxidative stress level. Then, the redox homeostasis changes inactivated NF-κB pathway by impeding iKBα ubiquitination and blocking nuclear translocation of NF-κB P65, and then triggered the damping of M1 macrophage polarization. Notably, miR-19-EXO also outperformed lentiviral miR-19b-3p or shp47phox delivery and conventional ROS scavengers in synergistic biological functions. Our finding paves the way of engineering ADSC-EXO to develop a proactive intervention strategy for ALF by increasing its specificity and functionality.

Keywords:  ADSCs; Acute liver failure; Exosomes; Microenvironment remodeling; Nanomedicine

DOI:  https://doi.org/10.1016/j.mtbio.2025.102697
Theriogenology. 2026 Jan 14. pii: S0093-691X(26)00021-X. [Epub ahead of print]255 117831

Nano-delivery system of milk-derived exosomes loaded with Forsythiaside A: Studies on bovine mammary epithelial cells and mastitis induced mice.

Xiaoqing Yang, Yangyang Pan, Meng Wang, Xin Ma, Xiaohong Han, Tianhao Li, Shanshan Yang, Jianying Chang, Hanxun Liu, Sijiu Yu, Yan Cui.

  Bovine mammary gland health is essential for sustaining milk yield and dairy production efficiency. Currently, antimicrobial resistance resulting from antibiotic treatment of mastitis severely constrains the sustainable development of the dairy industry. Forsythoside A (FTA), a natural phenylethanoid glycoside possessing potent anti-inflammatory and antioxidant activities, exhibits considerable therapeutic potential; however, its clinical translation remains hindered by poor bioavailability. To address this limitation, a milk-derived exosome-based nano-delivery system (FTA-mExos) was engineered. The therapeutic efficacy and underlying mechanisms of FTA-mExos were systematically evaluated in both in vitro and in vivo inflammatory models established using clinically isolated Staphylococcus chromogenes (S. chromogenes). In vitro, FTA-mExos significantly reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels in S. chromogenes-infected bovine mammary epithelial cells (BMECs), while enhancing glutathione peroxidase (GSH-Px) activity and restoring mitochondrial membrane potential. Mechanistically, FTA-mExos alleviated inflammatory responses by suppressing NF-κB signaling and downregulating the expression of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α. In vivo studies revealed that FTA-mExos upregulated the expression of tight junction proteins (ZO-1, Occludin, and Claudin-3), leading to the restoration of blood-milk barrier (BMB) integrity and attenuation of oxidative stress injury and inflammatory responses. These findings demonstrate that FTA-mExos represent a promising nano-delivery strategy for the treatment of bovine mastitis.

Keywords:  Blood-milk barrier; Forsythoside A; Milk-derived exosomes; NF-κB; Staphylococcus chromogenes; Tight junction

DOI:  https://doi.org/10.1016/j.theriogenology.2026.117831
Pharm Sci Adv. 2025 Dec;3 100075

Homologous tumor cell exosome-based drug delivery system co-delivering temozolomide and resveratrol for orthotopic glioblastoma therapy.

Xuemei Wang, Tao Zhang, Dandan Zhang, Yuxin Cao, Xinxin Wang, Xiaowei Liu, Weili Yang, Yingchao Liu, Daquan Chen.

  Temozolomide (TMZ) is the first-line chemotherapeutic agent for treating glioblastoma multiforme (GBM), but its potency is hampered by inevitable drug resistance and systematic toxicity. Novel strategies that can decrease drug-associated adverse events are urgently needed. Encouraged by the significant pro-apoptotic, anti-inflammatory, and anti-proliferative properties of resveratrol (RES), one of the most widely studied polyphenolic compounds in cancer therapy, we propose a synergistic therapeutic strategy by using the combination of TMZ and RES to inhibit GBM progression. Recently, exosomes (Exos) have received increasing attention as promising drug delivery alternatives with favorable intrinsic features. In this work, Exos derived from homologous U87 cells are developed to co-deliver TMZ/RES for GBM therapy, defined as U87-Exos@TMZ/RES. It is found that U87-Exos@TMZ/RES share various advantages, including intrinsic tumor-targeting accumulation with homologous effects, as well as enhanced antitumor activity with synergistic effects of TMZ and RES. Furthermore, the excellent therapeutic effect of U87-Exos@TMZ/RES is also achieved in orthotopic GBM models. Based on these results, this novel U87-Exos@TMZ/RES delivery platform can provide a promising systemic chemotherapy strategy for enhancing GBM treatment.

Keywords:  Combination therapy; Exosomes; Glioblastoma multiforme; Orthotopic models

DOI:  https://doi.org/10.1016/j.pscia.2025.100075