bims-engexo Biomed News
on Engineered exosomes
Issue of 2025–01–05
six papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Therapeutic Potential of Feline Adipose-Derived Stem Cell Exosomes in the Treatment of Feline Idiopathic Cystitis: A Characterization and Functional Analysis of miRNA Content.
  2. Exosomes as nature's nano carriers: Promising drug delivery tools and targeted therapy for glioma.
  3. Integrating oxygen-boosted sonodynamic therapy and ferroptosis via engineered exosomes for effective cancer treatment.
  4. Exosomes loaded with the anti-cancer molecule mir-1-3p inhibit intrapulmonary colonization and growth of human esophageal squamous carcinoma cells.
  5. A hyaluronic acid nanogels based exosome production factory for tumor photothermal therapy and angiogenesis inhibition.
  6. Curcumin-induced exosomal FTO from bone marrow stem cells alleviates sepsis-associated acute kidney injury by modulating the m6A methylation of OXSR1.
  1. Nanotheranostics. 2025 ;9(1): 38-51
    Therapeutic Potential of Feline Adipose-Derived Stem Cell Exosomes in the Treatment of Feline Idiopathic Cystitis: A Characterization and Functional Analysis of miRNA Content.
    Andrea Rubini, Federica Zanotti, Danilo Licastro, Giulia Calogero, Gisella Bettini, Cristiana Piccoli, Giuseppe Rubini, Luca Lovatti, Barbara Zavan.
      Feline Idiopathic Cystitis (FIC), is a chronic lower urinary tract condition in cats analogous to PBS/IC in women, which presents significant treatment challenges due to its idiopathic nature. Recent advancements in regenerative medicine highlight the potential of Adipose Tissue-Derived Stem Cells (ADSCs), particularly through their secretome, which includes mediators, bioactive molecules, and extracellular vesicles (EVs). Notably, exosomes, a subset of EVs, facilitate cell-to-cell communication and, when derived from ADSCs, exhibit anti-inflammatory properties and contribute to tissue regeneration. In this work, we aim to characterize the content of exosomes derived from feline ADSCs (fADSCs) to elucidate their mechanisms of action on recipient cells and assess their therapeutic potential for FIC. Exosomes were isolated from fADSCs and their microRNA (miRNA) content sequenced using Illumina technology. Our findings demonstrate that fADSC-derived exosomes harbor miRNAs that can induce regenerative processes, such as cell proliferation, immune modulation, angiogenesis, and anti-inflammatory responses. Key miRNAs identified include fca-miR-221, fca-let-7f-5p, fca-miR-337-5p, fca-miR-542-5p, fca-miR-24-3p, fca-miR-205, and fca-miR-23a, which promote proliferative, angiogenic, differentiation, and regenerative mechanisms. Additionally, miRNAs with anti-inflammatory effects, such as fca-miR-193a-5p and fca-miR-127-3p, and those positively regulating the immune system, including fca-let-7a-5p and fca-miR-chrC1_18846-5p, were identified. Of particular interest, fca-miR-219-5p (has-miR-6766-3p) has been reported to suppress liver fibrosis.These results underline the therapeutic potential of fADSC-derived exosomes in treating FIC and suggest innovative strategies for feline veterinary medicine.
    Keywords:  Exosomes; Feline Adipose-derived Mesenchymal Stem Cells (fADSCs); Innovative therapy; Veterinary Medicine; miRNAs
    DOI:  https://doi.org/10.7150/ntno.99383
  2. Biomed Pharmacother. 2024 Dec 27. pii: S0753-3322(24)01640-8. [Epub ahead of print]182 117754
    Exosomes as nature's nano carriers: Promising drug delivery tools and targeted therapy for glioma.
    Rashmi Rana, Shamjetsabam Nandibala Devi, Amit Kumar Bhardwaj, M H Yashavarddhan, Deepika Bohra, Nirmal Kumar Ganguly.
      Exosomes, minute vesicles originating from diverse cell types, exhibit considerable potential as carriers for drug delivery in glioma therapy. These naturally occurring nanocarriers facilitate the transfer of proteins, RNAs, and lipids between cells, offering advantages such as biocompatibility, efficient cellular absorption, and the capability to traverse the blood-brain barrier (BBB). In the realm of cancer, particularly gliomas, exosomes play pivotal roles in modulating tumor growth, regulating immunity, and combating drug resistance. Moreover, exosomes serve as valuable biomarkers for diagnosing diseases and assessing prognosis. This review aims to elucidate the therapeutic and diagnostic promise of exosomes in glioma treatment, highlighting the innovative advances in exosome engineering that enable precise drug loading and targeting. By circumventing challenges associated with current glioma treatments, exosome-mediated drug delivery strategies can enhance the efficacy of chemotherapy drugs like temozolomide and overcome drug resistance mechanisms. This review underscores the multifaceted roles of exosomes in glioma pathogenesis and therapy, underscoring their potential as natural nanocarriers for targeted therapy and heralding a new era of hope for glioma treatment.
    Keywords:  Blood-brain barrier; Drug delivery; Exosomes; Glioma; Targeted therapy
    DOI:  https://doi.org/10.1016/j.biopha.2024.117754
  3. Theranostics. 2025 ;15(1): 68-85
    Integrating oxygen-boosted sonodynamic therapy and ferroptosis via engineered exosomes for effective cancer treatment.
    Mingbo Wu, Zhanlin Zhang, Dong Li, Xiaomiao Ruan, Jingwen Yang, Siyi Chen, Xin Li, Wenwu Ling.
      Rationale: Ferroptosis and sonodynamic therapy (SDT) are both promising therapeutic modalities, but their clinical application remains challenging due to the hypoxic tumor microenvironment and limited supply of polyunsaturated fatty acids. Developing an agent with oxygen-enhanced SDT and increased ferroptosis sensitivity is crucial for advancing tumor therapy. Methods: In this study, catalase (Cat) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) highly expressed 4T1 cells were constructed via lentivirus transfection. Cat and ACSL4 enriched exosomes (EXO@CA) were then extracted and loaded with the sonosensitizer tetrakis (4-carboxyphenyl) porphyrin (TCPP) through electroporation to create engineered exosomes (EXO@CAT). We evaluated the ability of EXO@CAT to generate oxygen in a hydrogen peroxide environment and investigated its effect on motion profiles and permeability of EXO@CAT. The in vitro antitumor activity was assessed via cytotoxicity, ROS levels, live/dead staining, and apoptosis, with ferroptosis biomarkers confirming ferroptosis activation. We also evaluated the in vivo anticancer efficacy of EXO@CAT by tumor growth analysis and histological and immunohistochemical staining in mouse models bearing breast tumor. Results: EXO@CAT harnesses ultrasound stimulation to facilitate oxygen-enriched SDT, demonstrating significant capacity for singlet oxygen (1O2) generating, which promotes the accumulation of lipid peroxidation (LPO), ultimately leading to the induction of ferroptosis. Concurrently, ACSL4 released from EXO@CAT also increases LPO accumulation by modifying cellular lipid composition, thereby enhancing cellular sensitivity to ferroptosis. Moreover, both in vitro and in vivo experiments demonstrate that the homologous targeting ability of EXO@CAT enables its efficient accumulation in tumor tissues, and the oxygen generation catalyzed by Cat not only alleviates tumor hypoxia but also facilitates the penetration of EXO@CAT into deeper layers of tumor tissue. Conclusions: EXO@CAT combines endogenous proteins, which are prone to inactivation, with an exogenous sonosensitizer, allowing synergistic anticancer treatment of both ferroptosis and SDT with improved efficacy.
    Keywords:  Active penetration; Engineered exosome; Ferroptosis; Sonodynamic therapy; Tumor microenvironment
    DOI:  https://doi.org/10.7150/thno.102977
  4. J Transl Med. 2024 Dec 31. 22(1): 1166
    Exosomes loaded with the anti-cancer molecule mir-1-3p inhibit intrapulmonary colonization and growth of human esophageal squamous carcinoma cells.
    Yanmei Yu, Bingjie Jin, Ruzhen Jia, Lei Shi, Yong Chen, Jian Ge, Changqin Xu.
       BACKGROUND: The overall prognosis of patients with esophageal cancer (EC) is extremely poor. There is an urgent need to develop innovative therapeutic strategies. This study will investigate the anti-cancer effects of exosomes loaded with specific anti-cancer microRNAs in vivo and in vitro.
    METHODS: Specific miRNAs that were significantly down-regulated in EC tissues were screened using the miRNAs profiling data of human EC tissue samples in TCGA, and the role of their exogenous expression in the proliferation and migration of human EC cell lines, KYSE150 and Eca109, were detected using CCK-8 and Transwell assays. Exosomes were loaded with miRNAs using electroporation.
    RESULTS: The expression of miR-1-3p was significantly down-regulated in human EC tissues with potential anti-cancer effects. Exosomes loaded with miR-1-3p significantly inhibited the proliferation, migration and invasion of KYSE150 and Eca109 cells in vitro, as well as the intrapulmonary colonization and growth of KYSE150 cells in vivo. In addition, miR-1-3p could directly bind to the 3'UTR of the transcription factor E2F5 mRNA, down-regulate the protein expression of E2F5, and inhibit the activation of the MAPK/ERK signaling pathway.
    CONCLUSION: Exosomes loaded with miR-1-3p may be applicable to the treatment of EC.
    Keywords:  Esophageal squamous carcinoma; Exosomes; Gene therapy; MicroRNA; Nanocarriers
    DOI:  https://doi.org/10.1186/s12967-024-05997-9
  5. Int J Biol Macromol. 2024 Dec 30. pii: S0141-8130(24)10174-2. [Epub ahead of print] 139363
    A hyaluronic acid nanogels based exosome production factory for tumor photothermal therapy and angiogenesis inhibition.
    Tong Wu, Huijuan Song, Rijie Wang, Weiwei Wang, Jinfeng Xing.
      Exosomes as a unique drug delivery system provide a new choice for tumor therapy. However, the in vitro functionalization of exosomes and the process of circulating drug delivery can easily cause exosome degradation and drug loss, thus reducing the efficiency of drug delivery. In this work, based on the endocyto-fusion-exocytosis pathway of exosome formation, a multifunctional hyaluronic acid nanogel loaded with the antiangiogenic drug vatalanib and the near-infrared photothermal agent indocyanine green (ICG) was designed. Lysosome escape and photothermal therapy were combined to promote exosome production. Hyaluronic acid nanogels were endocytosed by tumor cells with CD44 mediation, forming intracellular vesicle-coated nanogels, which were subsequently degraded by hyaluronidase with high expression in tumor cells. Anti-angiogenic signals in intracellular vesicles were then delivered to vascular endothelial cells by exosomes through membrane fusion and exocytosis, which inhibited tumor angiogenesis to prevent tumor proliferation and metastasis. Cell experiments and tumor models demonstrate that our therapeutic strategy can achieve effective tumor inhibition.
    Keywords:  Exosome; Hyaluronic acid nanogels; Lysosome escape
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139363
  6. Kaohsiung J Med Sci. 2024 Dec 30. e12923
    Curcumin-induced exosomal FTO from bone marrow stem cells alleviates sepsis-associated acute kidney injury by modulating the m6A methylation of OXSR1.
    Ting Yang, Hui Yu, Zheng Xie.
      Curcumin and bone marrow stem cells (BMSCs)-derived exosomes are considered to be useful for the treatment of many human diseases, including sepsis-associated acute kidney injury (SA-AKI). However, the role and underlying molecular mechanism of curcumin-loaded BMSCs-derived exosomes in the progression of SA-AKI remain unclear. Exosomes (BMSCs-EXOCurcumin or BMSCs-EXOControl) were isolated from curcumin or DMSO-treated BMSCs, and then co-cultured with LPS-induced HK2 cells. Cell proliferation and apoptosis were determined by cell counting kit 8 (CCK8) assay, 5-ethynyl-2-deoxyuridine (EdU) assay, and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used for examining inflammatory factors. The levels of SOD, MDA, and ROS were tested to assess oxidative stress. The levels of fat mass and obesity-associated protein (FTO) and oxidative stress responsive 1 (OXSR1) were detected by quantitative real-time PCR and western blot. Methylated RNA immunoprecipitation (MeRIP) assay and RNA immunoprecipitation (RIP) assay were used for measuring the interaction between FTO and OXSR1. BMSCs-EXOCurcumin treatment could inhibit LPS-induced HK2 cell apoptosis, inflammation, and oxidative stress. FTO was downregulated in SA-AKI patients and LPS-induced HK2 cells, while was upregulated in BMSCs-EXOCurcumin. Exosomal FTO from curcumin-induced BMSCs suppressed apoptosis, inflammation, and oxidative stress in LPS-induced HK2 cells. FTO decreased OXSR1 expression through m6A modification, and the inhibitory effect of FTO on LPS-induced HK2 cell injury could be eliminated by OXSR1 overexpression. In animal experiments, BMSCs-EXOCurcumin alleviated kidney injury in SA-AKI mice models by regulating FTO/OXSR1 axis. In conclusion, exosomal FTO from curcumin-induced BMSCs reduced OXSR1 expression to alleviate LPS-induced HK2 cell injury and improve kidney function in CLP-induced mice models, providing a new target for SA-AKI.
    Keywords:  FTO; OXSR1; bone marrow stem cells; exosomes; sepsis‐associated AKI
    DOI:  https://doi.org/10.1002/kjm2.12923
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