bims-engexo 2024-07-21 papers

Issue of 2024‒07‒21
four papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

MedComm (2020). 2024 Aug;5(8): e660

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases.

Chuan Xu, Chaoyang Jiang, Zhihui Li, Hui Gao, Jing Xian, Wenyan Guo, Dan He, Xingchen Peng, Daijun Zhou, Dong Li.

Exosomes are nanoscale vesicles of cellular origin. One of the main characteristics of exosomes is their ability to carry a wide range of biomolecules from their parental cells, which are important mediators of intercellular communication and play an important role in physiological and pathological processes. Exosomes have the advantages of biocompatibility, low immunogenicity, and wide biodistribution. As researchers' understanding of exosomes has increased, various strategies have been proposed for their use in diagnosing and treating diseases. Here, we provide an overview of the biogenesis and composition of exosomes, describe the relationship between exosomes and disease progression, and focus on the use of exosomes as biomarkers for early screening, disease monitoring, and guiding therapy in refractory diseases such as tumors and neurodegenerative diseases. We also summarize the current applications of exosomes, especially engineered exosomes, for efficient drug delivery, targeted therapies, gene therapies, and immune vaccines. Finally, the current challenges and potential research directions for the clinical application of exosomes are also discussed. In conclusion, exosomes, as an emerging molecule that can be used in the diagnosis and treatment of diseases, combined with multidisciplinary innovative solutions, will play an important role in clinical applications.

Keywords: drug delivery; exosome; immunotherapy; liquid biopsy; targeted therapies

DOI: https://doi.org/10.1002/mco2.660

Front Cardiovasc Med. 2024 ;11 1399738

Engineered exosomes: a potential therapeutic strategy for septic cardiomyopathy.

Lixia Mao, Songtao Liu, Yongxia Chen, Huiyi Huang, Fenghua Ding, Liehua Deng.

Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.

Keywords: drug delivery; engineered exosomes; extracellular vesicles; sepsis; septic cardiomyopathy

DOI: https://doi.org/10.3389/fcvm.2024.1399738

Burns Trauma. 2024 ;12 tkae023

Engineered exosomes as a prospective therapy for diabetic foot ulcers.

Lifei Guo, Dan Xiao, Helin Xing, Guodong Yang, Xuekang Yang.

Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.

Keywords: Diabetic angiopathy; Diabetic foot; Diabetic peripheral neuropathy; Engineered exosomes; Foot ulcer; Inflammation; Re-epithelialization; Wound healing; Wound infection

DOI: https://doi.org/10.1093/burnst/tkae023

Acta Pharm Sin B. 2024 Jul;14(7): 3009-3026

Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors.

The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads. NAF-derived EXs (NAF-EXs) were used for loading ormeloxifene (ORM), a potent anti-cancer and desmoplasia inhibitor as a model drug. We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype, which may be due to regulation of Ca2+ influx in fibroblast cells. NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition (EMT) and repressed tumor growth in xenograft mouse model. In conclusion, our data suggests preferential tropism of NAF-EXs for PDAC tumors, thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs. Additionally, it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

Keywords: Desmoplasia; Exosomes; Extracellular vesicles; Ormeloxifene; Pancreatic cancer; Personalized medicine; Tumor adjacent normal tissue fibroblasts (NAF); Tumor targeting

DOI: https://doi.org/10.1016/j.apsb.2024.04.003