bims-engexo Biomed News
on Engineered exosomes
Issue of 2024–09–29
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur
  1. Engineered extracellular vesicles with polypeptide for targeted delivery of doxorubicin against EGFR‑positive tumors.
  2. Engineered macrophage-derived exosomes via click chemistry for the treatment of osteomyelitis.
  3. Landscape of exosomes to modified exosomes: a state of the art in cancer therapy.
  4. Extracellular Vesicle-Derived Non-Coding RNAs: Key Mediators in Remodelling Heart Failure.
  5. Modified bone marrow mesenchymal stem cells derived exosomes loaded with MiRNA ameliorates non-small cell lung cancer.
  6. miR‑25‑3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function.
  7. Targeting SNAI1-Mediated Colorectal Cancer Chemoresistance and Stemness by Sphingosine Kinase 2 Inhibition.
  1. Oncol Rep. 2024 Nov;pii: 154. [Epub ahead of print]52(5):
    Engineered extracellular vesicles with polypeptide for targeted delivery of doxorubicin against EGFR‑positive tumors.
    Yuqing Yang, Fang Wang, Yuqin Li, Ruxi Chen, Xiangyu Wang, Jiahong Chen, Xi Lin, Haipeng Zhang, Youwei Huang, Rui Wang.
      Lack of effective tumor‑specific delivery systems remains an unmet clinical challenge for the employment of chemotherapy using cytotoxic drugs. Extracellular vesicles (EVs) have recently been investigated for their potential as an efficient drug‑delivery platform, due to their good biodistribution, biocompatibility and low immunogenicity. In the present study, the formulation of GE11 peptide‑modified EVs (GE11‑EVs) loaded with doxorubicin (Dox‑GE11‑EVs), was developed to target epidermal growth factor receptor (EGFR)‑positive tumor cells. The results obtained demonstrated that GE11‑EVs exhibited highly efficient targeting and drug delivery to EGFR‑positive tumor cells compared with non‑modified EVs. Furthermore, treatment with Dox‑GE11‑EVs led to a significantly inhibition of cell proliferation and increased apoptosis of EGFR‑positive tumor cells compared with Dox‑EVs and free Dox treatments. In addition, it was observed that treatment with either free Dox or Dox‑EVs exhibited a high level of cytotoxicity to normal cells, whereas treatment with Dox‑GE11‑EVs had only a limited effect on cell viability of normal cells. Taken together, the findings of the present study demonstrated that the engineered Dox‑GE11‑EVs can treat EGFR‑positive tumors more accurately and have higher safety than traditional tumor therapies.
    Keywords:  EGFR‑positive cancer; chemotherapy; colorectal cancer; engineered extracellular vesicles; glioma; targeted drug delivery
    DOI:  https://doi.org/10.3892/or.2024.8813
  2. J Mater Chem B. 2024 Sep 24.
    Engineered macrophage-derived exosomes via click chemistry for the treatment of osteomyelitis.
    Yongfeng Chen, Jintao Dong, Jiahan Li, Jun Li, Yizhao Lu, Wengang Dong, Dawei Zhang, Xingbo Dang.
      Osteomyelitis is a severe bone condition caused by bacterial infection that can lead to lifelong disabilities or fatal sepsis. Given that the infection is persistent and penetrates deep into the bone tissue, targeting and rapidly treating osteomyelitis remain a significant challenge. Herein, a triblock targeting peptide featuring ROS-cleavable linkage/antibacterial/bone-targeting unit was grafted onto the macrophage-derived exosomes (RAB-EXO). In vitro, the effective eradication of osteomyelitis pathogens MRSA/E. coli and induction of M2 macrophage differentiation were triggered by RAB-EXO. In vivo, after the intravenous administration of RAB-EXO, it can target the bone tissue and release antimicrobial peptides in the high ROS environment of osteomyelitis. The released antimicrobial peptides markedly inhibit bacterial growth at the infection sites. Moreover, M2 differentiation of the bone tissue macrophages are facilitated by EXO, thereby decreasing the inflammatory factors and achieving the anti-inflammatory effect. Finally, the complete healing of osteomyelitis without adverse effects associated with traditional treatments is achieved within 28 days in rat models. Our findings confirm that RAB-EXO, as a targeted treatment for osteomyelitis, offers promising directions for addressing other bacterial infection diseases, such as periodontitis and rheumatoid arthritis, through similar mechanisms.
    DOI:  https://doi.org/10.1039/d4tb01346h
  3. RSC Adv. 2024 Sep 24. 14(42): 30807-30829
    Landscape of exosomes to modified exosomes: a state of the art in cancer therapy.
    Divya Mirgh, Swarup Sonar, Srestha Ghosh, Manab Deb Adhikari, Vetriselvan Subramaniyan, Sukhamoy Gorai, Krishnan Anand.
      Exosomes are a subpopulation of extracellular vesicles (EVs) that naturally originate from endosomes. They play a significant role in cellular communication. Tumor-secreted exosomes play a crucial role in cancer development and significantly contribute to tumorigenesis, angiogenesis, and metastasis by intracellular communication. Tumor-derived exosomes (TEXs) are a promising biomarker source of cancer detection in the early stages. On the other hand, they offer revolutionary cutting-edge approaches to cancer therapeutics. Exosomes offer a cell-free approach to cancer therapeutics, which overcomes immune cell and stem cell therapeutics-based limitations (complication, toxicity, and cost of treatment). There are multiple sources of therapeutic exosomes present (stem cells, immune cells, plant cells, and synthetic and modified exosomes). This article explores the dynamic source of exosomes (plants, mesenchymal stem cells, and immune cells) and their modification (chimeric, hybrid exosomes, exosome-based CRISPR, and drug delivery) based on cancer therapeutic development. This review also highlights exosomes based clinical trials and the challenges and future orientation of exosome research. We hope that this article will inspire researchers to further explore exosome-based cancer therapeutic platforms for precision oncology.
    DOI:  https://doi.org/10.1039/d4ra04512b
  4. Curr Issues Mol Biol. 2024 Aug 27. 46(9): 9430-9448
    Extracellular Vesicle-Derived Non-Coding RNAs: Key Mediators in Remodelling Heart Failure.
    Jiayi Zhao, Huang Huang.
      Heart failure (HF), a syndrome of persistent development of cardiac insufficiency due to various heart diseases, is a serious and lethal disease for which specific curative therapies are lacking and poses a severe burden on all aspects of global public health. Extracellular vesicles (EVs) are essential mediators of intercellular and interorgan communication, and are enclosed nanoscale vesicles carrying biomolecules such as RNA, DNA, and proteins. Recent studies have showed, among other things, that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long ncRNAs (lncRNA), and circular RNAs (circRNAs) can be selectively sorted into EVs and modulate the pathophysiological processes of HF in recipient cells, acting on both healthy and diseased hearts, which makes them promising targets for the diagnosis and therapy of HF. This review aims to explore the mechanism of action of EV-ncRNAs in heart failure, with emphasis on the potential use of differentially expressed miRNAs and circRNAs as biomarkers of cardiovascular disease, and recent research advances in the diagnosis and treatment of heart failure. Finally, we focus on summarising the latest advances and challenges in engineering EVs for HF, providing novel concepts for the diagnosis and treatment of heart failure.
    Keywords:  biogenesis; engineered extracellular vesicles; exosome; extracellular vesicles; heart failure; microRNA; non-coding RNA
    DOI:  https://doi.org/10.3390/cimb46090559
  5. J Cell Mol Med. 2024 Sep;28(18): e70115
    Modified bone marrow mesenchymal stem cells derived exosomes loaded with MiRNA ameliorates non-small cell lung cancer.
    Mingjun Yang, Wen Zhou, Xiao Han, Mingming Xu, Zhipeng Wang, Min Shi, Yanyan Shi, Yunchi Yu.
      The study aimed to reveal the function of LXY30 peptide-modified bone marrow mesenchymal stem cell-derived exosomes (LXY30-Exos) in NSCLC. LXY30 peptide is a peptide ligand targeting α3β1 integrin, and LXY30 specifically binds to Exos derived from different cells. We use transmission electron microscopy to identify LXY30-Exos and tracking analysis for particles, and the LXY30-Exos internalized by NSCLC cells in vitro and targeted NSCLC tumours in vivo were verified by multiple molecular technologies. The functions of LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 were assessed using cell proliferation, migration and cell apoptosis assays. Meanwhile, the safety of the above engineered Exos was evaluated in vivo. After LXY30-Exos were isolated and identified, LXY30-Exos were confirmed to be internalized by NSCLC cells in vitro and specifically targeted NSCLC tumours in vivo. Functionally, LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 weakened the proliferation, migration and cell cycle of NSCLC cells induced cellular apoptosis in vitro and restrained the tumour progression in vivo. Meanwhile, the safety of LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 was confirmed in vivo. Overall, miR-30c, miR-181b and miR-613 encapsulated in LXY30 peptide-modified BMSC-Exos relieved NSCLC.
    Keywords:  LXY30 peptide; exosomes; miR‐30c, miR‐181b and miR‐613; non‐small cell lung cancer
    DOI:  https://doi.org/10.1111/jcmm.70115
  6. Oncol Rep. 2024 Nov;pii: 153. [Epub ahead of print]52(5):
    miR‑25‑3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function.
    Yanbin Chen, Bingchen Chen, Shiliang Tu, Hang Yuan.
      Accumulating evidence indicates that the dysregulation of microRNAs (miRNAs or miRs), is associated with human malignancies and suggests a casual role of miRNAs in tumor initiation and progression. Even though it has been discovered that a number of miRNAs play significant parts in the development of colorectal cancer (CRC), it is crucial to comprehend the regulatory functions that other miRNAs play in CRC. Based on GSE183437 and GSE156719 microarray data that were obtained from Gene Expression Omnibus database, candidate miRNAs were researched. The oncogenic effects of miR‑25‑3p in different malignancies have led to its selection for additional investigation in the present study. The expression of miR‑25‑3p was verified by reverse transcription‑quantitative PCR, and its correlation with clinicopathological characteristics in patients with CRC was then investigated. In vitro assays were conducted to investigate the influence of miR‑25‑3p on the proliferative and apoptotic behaviors of HCT116 and Caco‑2 cells. The present data revealed that miR‑25‑3p exhibited one of the most significant upregulations in CRC tissues and cell lines. The expression levels of miR‑25‑3p were found to be intimately correlated with tumor size, distant metastasis, tumor‑node‑metastasis stage, and shorter overall survival rate. In terms of functionality, the downregulation of miR‑25‑3p led to the inhibition of cellular proliferation and the enhancement of apoptosis in both HCT116 and Caco‑2 cell lines. The critical tumor suppressor F‑box and WD repeat containing domain 7 (FBXW7) was identified as a direct molecular target for miR‑25‑3p, with an inverse relationship observed between the two in neoplastic tissues. Subsequent studies demonstrated that the tumor suppressive effects of miR‑25‑3p inhibitor were effectively negated by the silencing of FBXW7. Moreover, the ability of FBXW7 to inhibit the expression of several oncogenes was deemed essential for countering the anticancer effects mediated by miR‑25‑3p downregulation. These findings posit miR‑25‑3p as a promising therapeutic target and prognostic indicator for CRC.
    Keywords:  F‑box and WD repeat containing domain 7; cell apoptosis; cell proliferation; colorectal cancer; microRNA‑25‑3p
    DOI:  https://doi.org/10.3892/or.2024.8812
  7. World J Oncol. 2024 Oct;15(5): 744-757
    Targeting SNAI1-Mediated Colorectal Cancer Chemoresistance and Stemness by Sphingosine Kinase 2 Inhibition.
    Harinarayanan Janakiraman, Zachary Gao, Yun Zhu, Jiangling Dong, Scott A Becker, Alhaji Janneh, Besim Ogretmen, E Ramsay Camp.
       Background: Epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs), and colorectal cancer (CRC) therapy resistance are closely associated. Prior reports have demonstrated that sphingosine-1-phosphate (S1P) supports stem cells and maintains the CSC phenotype. We hypothesized that the EMT inducer SNAI1 drives S1P signaling to amplify CSC self-renewal capacity and chemoresistance.
    Methods: CRC cell lines with or without ectopic expression of SNAI1 were used to study the role of S1P signaling as mediators of cancer stemness and 5-fluorouracil (5FU) chemoresistance. The therapeutic ability of sphingosine kinase 2 (SPHK2) was assessed using siRNA and ABC294640, a SPHK2 inhibitor. CSCs were isolated from patient-derived xenografts (PDXs) and assessed for SPHK2 and SNAI1 expression.
    Results: Ectopic SNAI1 expressing cell lines demonstrated elevated SPHK2 expression and increased SPHK2 promoter activity. SPHK2 inhibition with siRNA or ABC294640 ablated in vitro self-renewal and sensitized cells to 5FU. CSCs isolated from CRC PDXs express increased SPHK2 relative to the non-CSC population. Combination ABC294640/5FU therapy significantly inhibited tumor growth in mice and enhanced 5FU response in therapy-resistant CRC patient-derived tumor organoids (PDTOs).
    Conclusions: SNAI1/SPHK2 signaling mediates cancer stemness and 5FU resistance, implicating S1P as a therapeutic target for CRC. The S1P inhibitor ABC294640 holds potential as a therapeutic agent to target CSCs in therapy refractory CRC.
    Keywords:  Cancer stem cells; Chemotherapy resistance; Colorectal cancer; Epithelial-to-mesenchymal transition; Sphingosine
    DOI:  https://doi.org/10.14740/wjon1890
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