bims-engexo 2025-06-29 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–06–29
ten papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered exosomes for targeted microRNA delivery to reverse liver fibrosis.
Bioinspired Nanoplatforms: Polydopamine and Exosomes for Targeted Antimicrobial Therapy.
Effects of dental pulp-derived mesenchymal stem cell exosomes produced under hypoxia conditions on osteoarthritic chondrocytes.
AntagomiR-192-5p-engineered exosomes encapsulated in MXene-modified GelMA hydrogel facilitated epithelization of burn wounds by targeting OLFM4.
Exosome-Mediated Mitochondrial Delivery of Antisense Oligonucleotides.
Extraction of anthocyanins from purple sweet potato: evaluation of anti-inflammatory effects in a rheumatoid arthritis animal model, mechanistic studies on inflammatory cells, and development of exosome-based delivery for enhanced targeting.
[Buyang Huanwu Decoction delays vascular aging in rats through exosomal miR-590-5p signal-mediated macrophage polarization].
Mesenchymal Stem Cell-Derived Exosomes in the Treatment of End-Stage Liver Disease.
Mechanistic insights into periodontal ligament stem cell-derived exosomes in tissue regeneration.
Dissecting Exosomal-Tumoral-Vascular Interactions of Single Tumor Cells and Clusters Using a Tumoral-Transendothelial Migration Chip.

Biomaterials. 2025 Jun 17. pii: S0142-9612(25)00429-6. [Epub ahead of print]324 123510

Engineered exosomes for targeted microRNA delivery to reverse liver fibrosis.

Huan Zhang, Jianming Xing, Man Sun, Yaxin Cui, Yulai Li, Siyuan Hu, Xinhe Wang, Hao Jiang, Yun Zhang, Xuanjie Jiang, Fang Yang, Betty Y S Kim, Wen Jiang, Zhaogang Yang, Lesheng Teng.

  Despite the widespread use of nucleic acid drugs in liver fibrosis treatment, their therapeutic efficacy remains limited due to challenges in penetrating extracellular matrix (ECM) and effectively targeting activated hepatic stellate cells (aHSCs). Exosomes (Exos) have emerged as promising drug carriers; however, their clinical application is hindered by low yield, limited drug-loading capacity, and suboptimal delivery efficiency. To overcome these challenges, we developed a nanosecond pulsed microfluidic system (T-nsPMs) for the high-throughput production of engineered Exos. These Exos were co-modified with a 5HT1D antibody and CD47 protein (TCMExos) to construct a nanoscale drug delivery system for the targeted delivery of microRNA-29b (miR-29b). TCMExos effectively penetrated the ECM, evaded macrophage phagocytosis, and targeted aHSCs, enabling the precise release of miR-29b at the site of fibrosis. This led to the inhibition of hepatic stellate cells activation, as demonstrated by the significant downregulation of α-SMA, COL1A1, TIMP-1, and phosphorylated SMAD2 proteins. Moreover, TCMExos markedly reduced collagen fibers deposition, showing excellent antifibrotic efficacy. Mechanistic studies revealed that TCMExos exert their antifibrotic efficacy by suppressing the TGF-β/SMAD signaling pathway. In conclusion, this work presents a new strategy for liver fibrosis treatment, offering an efficient and targeted approach to overcome current therapeutic limitations.

Keywords:  Drug delivery system; Exosomes; Liver fibrosis; Microfluidic technology; Nucleic acid drugs

DOI:  https://doi.org/10.1016/j.biomaterials.2025.123510
Polymers (Basel). 2025 Jun 16. pii: 1670. [Epub ahead of print]17(12):

Bioinspired Nanoplatforms: Polydopamine and Exosomes for Targeted Antimicrobial Therapy.

Barathan Muttiah, Alfizah Hanafiah.

  Global growth in antimicrobial resistance (AMR) has accelerated the need for novel therapy beyond the scope of conventional antibiotics. In the last decade, polydopamine (PDA), a mussel-inspired polymer with redox capability, remarkable adhesion, and biocompatibility, has emerged as a universal antimicrobial coating with widespread uses. At the same time, extracellular vesicles (EVs) and particularly exosomes have gained prominence for their intrinsic cargo delivery and immune-modulating properties. Here, we summarize the synergistic value of PDA and exosome integration into multifunctional antimicrobial nanoplatforms. We discuss the inherent antimicrobial activity of PDA and exosomes; the advantages of PDA coating, including increased exosome stability, ROS generation, and surface functionalization; and current methodologies towards designing PDA-exosome hybrids. This review also mentions other antimicrobial polymers and nanocomposites that may be employed for exosome modification, such as quaternized chitosan, zwitterionic polymers, and polymer-metal composites. Most significant challenges, such as the maintenance of exosome integrity, coating uniformity, biocompatibility, scalability, and immunogenicity, are addressed. Finally, future research directions are highlighted, with emphasis on intelligent, stimulus-responsive coatings, AMP incorporation, and clinical translation. Collectively, this review underscores the promise of PDA-coated exosomes as potential antimicrobial therapeutics against AMR with potential applications in wound healing, implant protection, and targeted infection control.

Keywords:  antimicrobial resistance (AMR); exosomes; hybrid nanoplatforms; polydopamine (PDA); stimuli-responsive coatings

DOI:  https://doi.org/10.3390/polym17121670
Connect Tissue Res. 2025 Jun 24. 1-13

Effects of dental pulp-derived mesenchymal stem cell exosomes produced under hypoxia conditions on osteoarthritic chondrocytes.

Habip Karaturk, Zeynep Burcin Gonen, Recep Saraymen, Nur Seda Gokdemir, Hasan Salkin.

   PURPOSE: Osteoarthritis is a common cause of disability worldwide. Exosomes are extracellular vesicles and can exert paracrine and endocrine actions. DPSCs exosomes offer a new avenue of research that may elucidate various functions related to cell proliferation, differentiation, and immunomodulation. We hypothesized that DPSC exosomes produced under hypoxia-induced culture conditions may have an anti-inflammatory effect on osteoarthritic chondrocytes and may re-regulate the inflammatory response that is increased in osteoarthritis. We also hypothesized that the decreased glycosaminoglycan production in osteoarthritis may be re-induced by DPSC exosomes produced under hypoxia.
MATERIALS AND METHODS: Exosomes were isolated from DPSCs under hypoxic (3% O2) and normoxic conditions (21% O2) separately and were applied to OA chondrocyte cells. Quantification, morphology and analysis of tetraspanin markers were performed to characterize the exosomes. After the OA chondrocytes were treated with exosomes for 48 hours, they were prepared for cell proliferation, apoptosis, viability, glycosaminoglycan tests, and inflammatory cytokine analysis.
RESULTS: Our results show that the pro-inflammatory cytokines were significantly suppressed in osteoarthritic chondrocytes by DPSC exosomes produced under hypoxia (p < 0.05). Exosomes of DPSCs grown in a hypoxia environment dramatically increase the amount of GAG in OA chondrocytes, giving clues that they can be used in cartilage regeneration (p < 0.001).
CONCLUSION: Considering that OA is associated with inflammatory components, DPSC exosome produced under hypoxic conditions prevents the formation of proinflammatory cytokines in osteoarthritic chondrocytes and shows therapeutic effects on osteoarthritic chondrocytes. Our study provides the first evidence showing the efficacy of DPSC-derived exosomes produced under hypoxia on osteoarthritic chondrocytes.

Keywords:  Osteoarthritis; dental pulp stem cells; exosome; hypoxia; inflammatory cytokine

DOI:  https://doi.org/10.1080/03008207.2025.2519064
Bioact Mater. 2025 Oct;52 318-337

AntagomiR-192-5p-engineered exosomes encapsulated in MXene-modified GelMA hydrogel facilitated epithelization of burn wounds by targeting OLFM4.

Wenzhang Liu, Hongchao Huang, Futing Shu, Yingying Liu, Jiezhi Lin, Lu Yang, Wei Zhang, Luofeng Jiang, Tianyi Liu, Chaoran Xie, Lei Li, Yin He, Shichu Xiao, Yongjun Zheng, Zhaofan Xia.

  Burn wound healing is a multifaceted process often complicated by excessive inflammation and impaired keratinocyte function, both of which are key factors contributing to delayed healing. In this study we screened the key miRNA regulating the epithelialization process under oxidative stress conditions through high-throughput sequencing. We identified that miR-192-5p was significantly upregulated in both oxidative stress models of keratinocytes and burn wound tissues, with detrimental effects on keratinocyte proliferation, migration, and apoptosis. Inhibition of miR-192-5p enhanced epidermal cell function by upregulating olfactomedin-4 (OLFM4), a key gene associated with cell proliferation, adhesion and migration. To optimize delivery and therapeutic efficacy, we engineered MSC-derived exosomes loaded with antagomiR-192-5p (ant-192; Final content: 2 nmol per wound; Loading efficiency: 35.22 ± 0.34 %) and then encapsulated into a composite hydrogel composed of GelMA and MXene (Ti3C2Tx) nanosheets, forming a multifunctional dressing (Exo-ant-192@M-Gel). It achieved sustained release of ant-192, delay its degradation, and exert anti-inflammatory properties, thus promoting epithelization and burn wound healing. This study offered a novel therapeutic approach for burn wound closure.

Keywords:  Exosome; GelMA; MXene; OLFM4; miR-192-5p

DOI:  https://doi.org/10.1016/j.bioactmat.2025.06.013
Nucleic Acid Ther. 2025 Jun 18.

Exosome-Mediated Mitochondrial Delivery of Antisense Oligonucleotides.

Dora von Trentini, Ivan J Dmochowski.

  We present a general method for in-cellulo delivery of 2'-O-methyl (2'-OMe) RNA oligonucleotides (oligos) to mitochondria for antisense applications, with potential for implementation in other mitochondrial DNA (mtDNA)-targeted therapies. Exosomes, which are nanoscale, naturally occurring extracellular vesicles (EVs), have been employed for biotechnology applications in oligonucleotide delivery in recent years. We discovered that exosomes from fetal bovine serum (FBS) can be used as a simple and biologically compatible delivery agent of 2'-OMe RNA antisense oligonucleotides to cellular mitochondria, leading to target protein knockdown. While most RNA interference and antisense mechanisms occur in the cytoplasm or nucleus, the need for mitochondrial targeting has become increasingly apparent. Mitochondrial disease describes a variety of currently incurable syndromes that especially affect organs requiring significant energy including the muscles, heart, and brain. Many of these syndromes result from mutations in mtDNA, which codes for the 13 proteins of the oxidative phosphorylation system and are thus often implicated in inherited metabolic disorders.

Keywords:  2′-OMe RNA; antisense oligonucleotides; exosome-based delivery; extracellular vesicles; fetal bovine serum; mitochondrial localization

DOI:  https://doi.org/10.1089/nat.2024.0067
Front Immunol. 2025 ;16 1559874

Extraction of anthocyanins from purple sweet potato: evaluation of anti-inflammatory effects in a rheumatoid arthritis animal model, mechanistic studies on inflammatory cells, and development of exosome-based delivery for enhanced targeting.

Jingjian Dong, Yuntao Lv, Cailiang Zhao, Yuanrui Shi, Ruiming Tang, Liheng He, Ruiwen Fan, Xiaoyun Jia.

   Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by inflammation and joint damage. Anthocyanins, such as those from purple sweet potato are known for their anti-inflammatory effects.
Methods: This study evaluated purple sweet potato anthocyanins (PSPA) therapeutic potential in RA using Human RA cells (MH7A) and collagen-induced arthritis (CIA) rat models. Rats were divided into control, CIA model, and three PSPA treatment groups (10, 20, 40 mg/kg) for 14 days. Meanwhile, exosomes were extracted from MH7A cells and loaded with PSPA, then co-incubated with inflammatory cells to observe the targeting capability of the drug-loaded exosomes.
Results: PSPA significantly reduced joint swelling and structural damage in CIA rats, with the highest dose (40 mg/kg) reducing tissue hyperplasia and inflammatory infiltration. PSPA also altered the gut microbiota, increasing beneficial bacteria like Akkermansia and Lactobacillus. Molecular analysis showed reduced serum levels of inflammatory cytokines TNF-α, IL-1β, and rheumatoid factor (RF). In MH7A cells, PSPA decreased inflammatory cytokines (IL-1α, IL-6, IL-18), inhibited cell proliferation (IC50 = 1.43 μg/mL), and induced apoptosis by modulating Bcl-2, Bax, Caspase-3, and Caspase-9. PSPA also restored the PI3K/AKT signaling pathway, reversing the suppression seen in CIA models, particularly at 40 mg/kg. Flow cytometry and microscopy confirmed dose-dependent apoptosis and cell cycle modulation. Meanwhile the PSPA-loaded exosomes demonstrated a high targeting capability toward inflammatory cells.
Conclusion: These findings indicate that PSPA can alleviate RA symptoms by reducing inflammation, modulating gut microbiota, and promoting apoptosis in synovial fibroblasts, with exosome-encapsulated anthocyanins enhancing its targeting efficiency.

Keywords:  anthocyanin; exosomes; gut microbiome; purple sweet potato; rheumatoid arthritis

DOI:  https://doi.org/10.3389/fimmu.2025.1559874
Nan Fang Yi Ke Da Xue Xue Bao. 2025 Jun 20. pii: 1673-4254(2025)06-1251-09. [Epub ahead of print]45(6): 1251-1259

[Buyang Huanwu Decoction delays vascular aging in rats through exosomal miR-590-5p signal-mediated macrophage polarization].

Shuyu Tu, Xiangyu Chen, Chenghui Li, Danping Huang, Li Zhang.

   OBJECTIVES: To investigate the mechanism underlying the inhibitory effect of Buyang Huanwu Decoction (BYHWD) on vascular aging.
METHODS: Eighteen male SD rats were randomized into young group, intraperitoneal D-galactose injection-induced aging group, and BYHWD gavage group. The changes in pulse wave velocity (PWV), vascular SA-β-gal activity, and expressions of p16, p21 and SA‑β‑gal of the rats were examined. Serum exosomes were isolated from the rats, and after characterization using NTA and TEM and for surface markers and vascular cell markers, were examined for miR-590-5p expression using qRT-PCR. The M1/M2 macrophage ratio and cytokine levels were evaluated using immunofluorescence staining and qRT-PCR. Bioinformatics analysis and dual-luciferase reporter assays were carried out to predict the potential target genes of miR-590-5p and validate its targeting relationship with SLC8A3, whose expressions were detected in the vascular tissues of the rats by Western blotting.
RESULTS: Compared with the young rats, the aging rats exhibited significantly increased PWV in the abdominal aorta with elevated vascular expressions of p16, p21 and SA-β-gal, which were all reversed by BYHWD treatment. The isolated serum exosomes were positive for CD63, CD81, CD31 and SM-22, and the exosomes from aging rats showed significantly downregulated expression of miR-590-5p, which was upregulated after BYHWD treatment. The aging rat vessels showed an increased M1/M2 macrophage ratio with elevated M1-specific cytokines and reduced M2-specific cytokines, and BYHWD treatment effectively inhibited M1 polarization of the macrophages. Pearson analysis revealed a negative correlation between exosomal miR-590-5p upregulation and the M1/M2 ratio. Bioinformatics analysis and dual-luciferase assays confirmed that miR-590-5p targets SLC8A3. Western blotting demonstrated increased SLC8A3 expression in aging rat vessels, which was downregulated after BYHWD treatment.
CONCLUSIONS: BYHWD attenuates vascular aging in rats by modulating macrophage M1 polarization and suppressing vascular inflammation via exosomal miR-590-5p-mediated downregulation of SLC8A3.

Keywords:  Buyang Huanwu Decoction; exosomes; macrophage polarization; miR-590-5p; vascular aging

DOI:  https://doi.org/10.12122/j.issn.1673-4254.2025.06.14
Curr Stem Cell Res Ther. 2025 Jun 20.

Mesenchymal Stem Cell-Derived Exosomes in the Treatment of End-Stage Liver Disease.

Fa-Da Wang, En-Qiang Chen.

  End-stage liver disease (ESLD) poses a significant threat to human health due to its high mortality rate. Although liver transplantation represents the most effective treatment modality, its application is limited by donor scarcity and prohibitive costs, thereby necessitating the development of innovative and efficacious therapeutic strategies. Within the realm of regenerative medicine, stem cell therapy has emerged as a promising alternative for ESLD treatment, with mesenchymal stem cells (MSCs) being at the forefront due to their exceptional multifunctional differentiation and self-renewal capabilities. Nonetheless, safety concerns, including the potential risk of tumorigenesis associated with MSCs, remain inadequately addressed. Recent evidence indicates that the therapeutic effects of MSCs are primarily mediated through paracrine mechanisms, with MSC-derived exosomes (MSC-Exos) serving as the principal effector mediators. The utilization of exosomes alone for therapeutic purposes not only preserves the beneficial effects of MSCs but also mitigates risks such as tumorigenic potential. Over the past few years, MSC-Exos have demonstrated significant ad-vancements across various medical disciplines, including cardiology, neurology, and gastroenterology. This review outlines the key mechanisms and recent progress in utilizing MSC-Exos in treating end-stage liver disease, seeking to highlight their unique therapeu- tic role.

Keywords:  End-stage liver disease; exosomes; hepatocellular carcinoma.; liver cirrhosis; liver injury; mesenchymal stem cells

DOI:  https://doi.org/10.2174/011574888X371122250613125926
Clin Oral Investig. 2025 Jun 25. 29(7): 357

Mechanistic insights into periodontal ligament stem cell-derived exosomes in tissue regeneration.

Paras Ahmad, Nathan Estrin, Nima Farshidfar, Yufeng Zhang, Richard J Miron.

   OBJECTIVE: This review comprehensively examined the emerging role of exosomes derived from periodontal ligament stem cells (PDLSC-Exos) in regenerative medicine and dentistry, with a particular focus on their therapeutic potential in periodontitis-a prevalent inflammatory disease characterized by the progressive destruction of periodontal tissues.
METHODS: An initial search on Scopus, Web of Science, and PubMed using terms associated with exosomes (i.e., exosomes, exosomal, extracellular vesicles, and EVs) and periodontal ligament stem cells without any limitation of publication year and field of study was performed on October 31st, 2024.
RESULTS: PDLSC-Exos demonstrated significant therapeutic efficacy in both bone and periodontal regeneration as well as various medical conditions through the enhancement of cellular proliferation, osteoblast differentiation, and the modulation of inflammatory responses. These exosomes function by regulating miRNA and activating essential signaling pathways, thereby facilitating periodontal/bone regeneration, angiogenesis, and tissue repair in disorders such as periodontitis, OTM, and skeletal bony defects. Furthermore, they exhibited anti-inflammatory properties, leading to improved outcomes under inflammatory conditions such as periodontitis, IBD, and MS. Moreover, PDLSC-Exos played a role in anti-microbial and anti-cancer interventions, demonstrating their diverse applicability.
CONCLUSION: The cell-free nature of these therapeutic agents makes PDLSC-Exos a versatile and promising tool for regenerative medicine and immune system regulation. The cell-free nature of these therapeutic agents positions PDLSC-Exos as a promising and adaptable instrument for regenerative medicine and immune system modulation.
CLINICAL RELEVANCE: PDLSC-Exos offer a promising acellular therapy for periodontal regeneration, overcoming limitations of cell-based approaches by enhancing tissue repair, modulating inflammation, and improving clinical translation in regenerative medicine and dentistry.

Keywords:  Exosomes; Periodontal ligament; Periodontium; Regeneration; Tissue engineering

DOI:  https://doi.org/10.1007/s00784-025-06422-1
ACS Nano. 2025 Jun 24.

Dissecting Exosomal-Tumoral-Vascular Interactions of Single Tumor Cells and Clusters Using a Tumoral-Transendothelial Migration Chip.

Xuan Zhang, Jun-Jie Bai, Shi-Cheng Fan, Lan-Feng Liang, Xiao Song, Mui Hoon Nai, Rui-Ping Zhang, Ming-Li Chen, Jian-Hua Wang, Chwee Teck Lim.

  The complex interplay between tumor cells and clusters with endothelial tissues during metastasis, in particular with regard to the exosomes in mediating intercellular communication, is still not well understood. Here, we develop a tumoral-transendothelial migration model to replicate the microenvironment of circulating tumor cells infiltrating blood vessels during metastasis. We propose an exosome-integrated approach combining a tumoral-transendothelial migration chip (TEMOC) with machine learning (ML) to enable the simulation and prediction of exosome-mediated invasion into the endothelial layer at both the single-cell and cluster levels. Leveraging a microfluidic trap array and the inherent self-organizing properties of cells, we conducted high-throughput studies on 121 specific tumor microenvironments on a chip. We uncovered the impact of exosomes derived from highly metastatic breast cancer on individual breast cancer cells and clusters: exosomes disrupt the adhesive matrix between endothelial cells and enhance tumor cell invasion. Additionally, highly metastatic cell-derived exosomes were found to stimulate the epithelial-mesenchymal transition (EMT) process in low-metastatic breast cancer cells (MCF-7), thereby promoting metastasis. An ML algorithm, K-nearest neighbor (KNN), was subsequently utilized to evaluate the correlation between multiple biomarkers on tumor cells and tumor invasion capability. The optimized biomarker combination strategy achieved a prediction accuracy of 93.5%. These findings contribute to a deeper understanding of the mechanisms by which exosomes derived from highly metastatic breast cancer cells induce metastasis. Furthermore, the combined use of the TEMOC and ML approach offers a platform for exploring the mechanisms of exosome-mediated tumor-vascular invasion and accelerating anti-metastatic therapeutic discovery.

Keywords:  cancer cells; endothelial cells; exosomes; metastasis; organ-on-a-chip

DOI:  https://doi.org/10.1021/acsnano.5c02557