bims-engexo 2025-07-20 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–07–20
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered exosomes with enriched miR-23b suppress the progression of periodontitis by reprogramming macrophages.
CD133+-Derived Exosomes Carrying EIF3B Mediate Cell Metastasis and Stemness in Colorectal Cancer.
Enhancing Skin Rejuvenation: Using of Engineered Exosome Content Treated With Oleuropein and Fe3O4@CQD/Oleuropein.
Recent advances in exosome-based nanodelivery systems for Parkinson's disease.
Treatment of non-small cell lung cancer using chem-bioinformatics-driven engineering of exosomal cargo-vehicle for telmisartan and pioglitazone targeted-delivery.
Exosomes derived from ALR-modified adipose mesenchymal stem cells mediate hepatoprotective effects on hepatic ischemia-reperfusion injury by promoting regeneration and protecting mitochondria.
Porcine umbilical cord exosomes promote regenerative skin repair through miR-192-5p/DSC1-mediated angiogenesis and collagen matrix optimization.

Colloids Surf B Biointerfaces. 2025 Jul 11. pii: S0927-7765(25)00454-0. [Epub ahead of print]255 114947

Engineered exosomes with enriched miR-23b suppress the progression of periodontitis by reprogramming macrophages.

Tianyuan Qiu, Zengguang Liu, Hugang Zhang, Jiaxin Jia, Xinxin Shao, Sihan Wang, Haobo Han, Quanshun Li, Min Hu.

  Periodontitis is a prevalent inflammatory disease that damages the tooth-supporting structure, leading to tooth instability and loss. Conventional therapies target biofilms but fail to address immune dysregulation, highlighting the need of host-modulating strategies. Herein, the decreased miR-23b level was found to be associated with the progression of periodontitis and identified as a potential therapeutic agent for the disease. Since the conventional methods of loading exogenous miRNAs into exosomes may impair the membrane structure, a miR-23b-overexpressed HEK293T cell line was constructed to produce engineered exosomes with enriched miR-23b (namely miR-23b-Exo). The miR-23b-Exo modulated the NF-κB signaling pathway in macrophages, thereby promoting the M2 polarization and suppressing the release of inflammatory cytokines to execute the anti-inflammatory effect. In rats with periodontitis, miR-23b-Exo alleviated the inflammation-induced periodontal damage, exhibiting favorable anti-periodontitis efficacy. Our study provides a promising host-modulating strategy based on the engineered exosomes-mediated miR-23b delivery, thereby alleviating periodontal damage by reprogramming macrophages.

Keywords:  Engineered exosomes; Inflammation; MiR-23b; NF-κB signaling pathway; Periodontitis

DOI:  https://doi.org/10.1016/j.colsurfb.2025.114947
Curr Cancer Drug Targets. 2025 Jul 11.

CD133+-Derived Exosomes Carrying EIF3B Mediate Cell Metastasis and Stemness in Colorectal Cancer.

Xiangwei Liao, Xiaodong Han, Yu Wang, Jun Yan, Zhenqian Wu.

   BACKGROUND: Colorectal cancer (CRC) is among the most widespread malignancies worldwide and is a leading cause for cancer mortality. The interstitial interaction between cancer and stem cells is important during cancer cell metastasis.
OBJECTIVE: In this study, we aimed to elucidate the regulatory role and the underlying mechanisms controlling the activity of exosomes derived from cancer stem cells (CSCs).
METHODS: Our group isolated exosomes from CSCs and non-CSCs to examine their regulatory mechanisms using Transwell migration, Cell Counting Kit-8 (CCK-8), and 5-ethynyl-2'-deoxyuridine (EdU) assays.
RESULTS: The role of Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) in CRC was examined using an in vivo tumorigenesis mouse model. It was found that treatment with exosomes isolated from CD133+ cells (CD133+Exos) promoted the proliferation and migration of SW480 cells. The downregulation of EIF3B reduced the proliferation and migration-promoting effects of CD133+ Exos on SW480 cells. Furthermore, CD133+ Exos treatment promoted the tumorigenesis of SW480 cells.
CONCLUSION: Our findings demonstrate that CSC-derived exosomes transport EIF3B into CRC cells to initiate epithelial-to-mesenchymal transition (EMT) and promote metastasis.

Keywords:  CD133<sup>+</sup>; EIF3B; Exosomes; colorectal cancer; digestive system.; intestinal neoplasms

DOI:  https://doi.org/10.2174/0115680096346009250628215410
J Cosmet Dermatol. 2025 Jul;24(7): e70351

Enhancing Skin Rejuvenation: Using of Engineered Exosome Content Treated With Oleuropein and Fe3O4@CQD/Oleuropein.

Naeimeh Safavizadeh, Zahra Noormohammadi, Mohammad Zaefizadeh, Kazem Nejati-Koshki.

   BACKGROUND: Skin aging, which is affected by intrinsic and extrinsic factors, leads to reduced elastin, collagen, and hydration levels.
AIMS: This study aimed to utilize modified exosomal content with treated Oleuropein and Fe3O4@C/Oleuropein to modulate gene and microRNA expression on the HFFF2 cells in vitro in order to reduce skin aging.
MATERIAL & METHODS: Fe3O4@C/Oleuropein was synthesized using the hydrothermal method and confirmed by XRD, FTIR, and SEM. The MTT assay was conducted to test toxicity Following this, hUC-MSCs and HFFF2 cells were treated with Fe3O4@C/Oleuropein and Oleuropein. Exosomes derived from the treatments were extracted by ultracentrifugation and evaluated by DLS and western blotting. HFFF2 cells were treated with exosomes derived from the treatments. The expression of the studied genes and related microRNAs was measured using qRT-PCR. Also, the effect of exosomes derived from the treatments on HFFF2 cells was evaluated using flow cytometry.
RESULTS: The results showed that the expression of IGF1, IGF1R, COL1A1, ELN, and EGF genes was significantly increased with Oleuropein (500 μg/mL) and Fe3O4@C/Oleuropein (250 μg/mL) treatments, especially when treated with exosomes derived from treatments. Moreover, the expression of hsa-miR-29b-3p, hsa-let-7d-5p, and hsa-let-7e-5p microRNAs was significantly downregulated, and hsa-miR-34a-5p was upregulated in the HFFF2 cells, which was consistent with the exosome cargo derived from treated cells.
CONCLUSIONS: Exosomes can increase gene expression and reduce microRNAs associated with skin antiaging. Using modified exosomal content treated with Oleuropein and Fe3O4@CQD/Oleuropein is generally effective for preventing skin aging and also presents innovative methods for skin care.

Keywords:  Fe3O4@CQD/oleuropein; microRNAs; modified exosomal content; oleuropein; skin rejuvenation

DOI:  https://doi.org/10.1111/jocd.70351
Biomaterials. 2025 Jul 10. pii: S0142-9612(25)00467-3. [Epub ahead of print]325 123548

Recent advances in exosome-based nanodelivery systems for Parkinson's disease.

Yongqiang Zhu, Qi Xi, Yan Liu, Yang Zhou, Jun Liao, Qiong Wu.

  Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects dopaminergic neurons in the substantia nigra. Its multifactorial pathogenic mechanisms include oxidative stress, mitochondrial dysfunction, α-synuclein aggregation, neuroinflammation, and alterations in the gut microbiome, ultimately leading to neuronal deficits and debilitating motor and nonmotor symptoms. Although conventional therapies provide temporary relief, their efficacy tends to wane over time or produce adverse effects. Exosome-based therapeutic strategies are a promising alternative, and we highlight the unique advantages of exosomes, including their biocompatibility, low immunogenicity, and ability to cross the blood-brain barrier, thereby facilitating the targeted delivery of neuroprotective and anti-inflammatory medications to affected regions. We also discuss recent advances in exosome engineering to improve cargo loading, enhance cell specificity and improve efficacy. However, large-scale exosome production, targeted delivery and long-term safety remain major challenges. Early-phase clinical trials of exosome-based therapies in other neurodegenerative conditions have demonstrated acceptable tolerability, and ongoing preclinical studies in PD models suggest potential efficacy, laying the groundwork for future clinical translation.

Keywords:  Exosomes; Nano drug delivery systems; Nanomedicine; Parkinson's disease; Target therapy

DOI:  https://doi.org/10.1016/j.biomaterials.2025.123548
Sci Rep. 2025 Jul 11. 15(1): 25166

Treatment of non-small cell lung cancer using chem-bioinformatics-driven engineering of exosomal cargo-vehicle for telmisartan and pioglitazone targeted-delivery.

Nadia M Hamdy, Eman F Sanad, Shaymaa E Kassab, Merhan Essam, Monica A Guirguis, Emad B Basalious, Ahmed S Sultan.

  The activation of the PPARG transcription factor is linked to reduced non-small cell lung cancer (NSCLC) growth. Bioinformatics, cheminformatics, and molecular docking/dynamics studies assessing pioglitazone and telmisartan as repurposed PPARG agonists for treating NSCLC with a targeted delivery system was done. Bioinformatics confirmed that the expression of the PPARG gene can predict outcomes in lung adenocarcinoma and is related to immune cells present in the tumor. Cheminformatics data showed that pioglitazone and telmisartan have a strong attraction to the PPARG receptor, with good efficiency as ligands. Both drugs were found to be lipophilic, suggesting compatibility with a targeted delivery formulation that may include albumin. Further cheminformatics predictions highlighted systemic toxicity values and the need for targeted delivery to minimize toxic side effects. Molecular docking and dynamics simulations showed that the telmisartan-MyoVc cargo domain complex was strong and stable during an 18 ns simulation period. Bioinformatics and cheminformatics data support pioglitazone and telmisartan as promising repurposed drugs for LUAC, highlighting their lipophilicity and compatibility with exosomal components like albumin. Cheminformatics also pointed out potential off-target effects and hepatotoxicity, emphasizing the importance of exosomal targeted delivery. Molecular docking and MD simulations confirmed the affinity and stability of drug-exosomal vehicle complexes. The proposed engineering of exosomal cargo for targeted delivery of these drugs to lung cells could enhance NSCLC treatment and address drug resistance while minimizing systemic toxicity.

Keywords:   Bioinformatics; Cheminformatics; Exosomes; In Silico drug repurposing; Lung adenocarcinoma; Molecular Docking; PPARG; Pioglitazone; Targeted delivery; Telmisartan

DOI:  https://doi.org/10.1038/s41598-025-10416-0
Stem Cell Res Ther. 2025 Jul 15. 16(1): 361

Exosomes derived from ALR-modified adipose mesenchymal stem cells mediate hepatoprotective effects on hepatic ischemia-reperfusion injury by promoting regeneration and protecting mitochondria.

YaJun Ma, Tao Liu, Pujun Li, Lei Cao, Xiangyu Lu, HongBin Wang.

   BACKGROUND: Exosomes are rich in bioactive molecules. Their unique lipid bilayer structure gives them the advantages of protecting the contents from degradation, easy cellular uptake, and good passive targeting. MSC-derived exosomes, which are natural vesicles ideal for gene delivery, exhibit a broad spectrum of therapeutic benefits.
METHODS: In this study, which combines cell-free therapy with gene therapy, adipose mesenchymal stem cells (ADSCs) were genetically modified with augmenter of liver regeneration (ALR) to derive exosomes overexpressing ALR, which were used as therapeutic agents in a miniature porcine model of laparoscopic hepatic ischemia‒reperfusion injury (IRI) combined with partial hepatectomy injury.
RESULTS: The findings of this study demonstrated that ALR-overexpressing adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) ameliorate hepatic tissue injury, reduce apoptosis, promote hepatic regeneration, and protect the integrity of the cellular mitochondrial structure and function.
CONCLUSIONS: In conclusion, ALR gene-modified ADSC-Exo strongly attenuate liver injury and promote liver tissue repair.

Keywords:  ADSC-Exo; ALR; Cell-free therapy; Gene therapy; Hepatic IRI; Miniature porcine

DOI:  https://doi.org/10.1186/s13287-025-04517-w
Biomater Adv. 2025 Jul 08. pii: S2772-9508(25)00234-1. [Epub ahead of print]177 214407

Porcine umbilical cord exosomes promote regenerative skin repair through miR-192-5p/DSC1-mediated angiogenesis and collagen matrix optimization.

Zhenhao Wen, Daiyu Zhang, Changfeng Yang, Junkai Hao, Qiang Pu, Taorun Luo, Jia Luo.

  The clinical application of human umbilical cord blood-derived exosomes (UCB-Exo) for wound healing is limited by ethical concerns and donor scarcity. To address these challenges, we propose porcine UCB-derived exosomes (PUCB-Exo) as an ethically acceptable alternative, which, when combined with a propolis complex (PC), demonstrates enhanced therapeutic efficacy. In a murine skin injury model, PUCB-Exo monotherapy significantly accelerated wound closure through the promotion of angiogenesis and modulation of extracellular matrix composition-specifically reducing excessive collagen deposition and optimizing the collagen I/III ratio compared to PBS controls. The combination therapy with PC further synergized this effect, resulting in superior tissue regeneration and wound repair outcomes compared to monotherapies. Transcriptomic profiling identified 26 differentially expressed genes (DEGs) in PUCB-Exo-treated wounds, predominantly associated with immune regulation and skin function pathways. Integrated miRNA-mRNA analysis highlighted miR-192-5p as a key regulatory molecule targeting DSC1, an essential component of desmosomal junctions involved in epidermal repair. Our findings establish PUCB-Exo as a promising substitute for UCB-Exo that overcomes translational barriers while offering improved scar management, supported by mechanistic insights into its synergistic interaction with natural product adjuvants.

Keywords:  Exosomes; Porcine; Skin wound healing; Umbilical cord blood; miRNA

DOI:  https://doi.org/10.1016/j.bioadv.2025.214407