bims-engexo 2024-10-27 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2024–10–27
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

From exosomes to mitochondria and myocardial infarction: Molecular insight and therapeutic challenge.
Target specification and therapeutic potential of extracellular vesicles for regulating corneal angiogenesis, lymphangiogenesis, and nerve repair.
Unveiling exosomes: Cutting-edge isolation techniques and their therapeutic potential.
miRNA packaging into small extracellular vesicles and implications in pain.
m6A-modified exosome-derived circHIF1α binding to KH domain of IGF2BP3 mediates DNA damage and arrests G1/S transition phase to resists bacterial infection in bacteremia.
Ultrasound-Driven Nanomachine for Enhanced Sonodynamic Therapy of Non-Small-Cell Lung Cancer.
Research progress of exosomes in pathogenesis and treatment of preeclampsia.

Pharmacol Res. 2024 Oct 18. pii: S1043-6618(24)00413-4. [Epub ahead of print]209 107468

From exosomes to mitochondria and myocardial infarction: Molecular insight and therapeutic challenge.

Chang Liu, Dengwen Zhang, Kekao Long, Wensheng Qi, Lei Pang, Jia Li, Kenneth King-Yip Cheng, Yin Cai.

  Myocardial infarction (MI) remains a leading cause of mortality worldwide. Despite patients with MI benefit from timely reperfusion therapies, the rates of mortality and morbidity remain substantial, suggesting an enduring need for the development of new approaches. Molecular mechanisms underlying myocardial ischemic injury are associated with both cardiomyocytes and non-cardiomyocytes. Exosomes are nano-sized extracellular vesicles released by almost all eukaryotic cells. They facilitate the communication between various cells by transferring information via their cargo and altering different biological activities in recipient cells. Studies have created great prospects for therapeutic applications of exosomes in MI, as demonstrated through their beneficial effect on heart function and reducing ventricular remodeling in association with fibrosis, angiogenesis, apoptosis, and inflammation. Of note, myocardial ischemic injury is primarily due to restricted blood flow, reducing oxygen availability, and causing inefficient utilization of energy substrates. However, the impact of exosomes on cardiac energy metabolism has not been adequately investigated. Although exosomes have been engineered for targeted delivery to enhance clinical efficacy, challenges must be overcome to utilize them reliably in the clinic. In this review, we summarize the research progress of exosomes for MI with a focus on the known and unknown regarding the role of exosomes in energy metabolism in cardiomyocytes and non-cardiomyocytes; as well as potential research avenues of exosome-mitochondrial energy regulation as well as therapeutic challenges. We aim to help identify more efficient molecular targets that may promote the clinical application of exosomes.

Keywords:  Cardiac energy metabolism; Exosome; Mitochondria; Myocardial infarction

DOI:  https://doi.org/10.1016/j.phrs.2024.107468
Ocul Surf. 2024 Oct 18. pii: S1542-0124(24)00111-3. [Epub ahead of print]34 459-476

Target specification and therapeutic potential of extracellular vesicles for regulating corneal angiogenesis, lymphangiogenesis, and nerve repair.

Cameron Pedersen, Victoria T Chen, Paula Herbst, Runze Zhang, Amr Elfert, Abhi Krishan, Dimitri T Azar, Jin-Hong Chang, Wen-Yang Hu, Tobias P Kremsmayer, Elmira Jalilian, Ali R Djalilian, Victor H Guaiquil, Mark I Rosenblatt.

Extracellular vesicles, including exosomes, are small extracellular vesicles that range in size from 30 nm to 10 μm in diameter and have specific membrane markers. They are naturally secreted and are present in various bodily fluids, including blood, urine, and saliva, and through the variety of their internal cargo, they contribute to both normal physiological and pathological processes. These processes include immune modulation, neuronal synapse formation, cell differentiation, cancer metastasis, angiogenesis, lymphangiogenesis, progression of infectious disease, and neurodegenerative disorders like Alzheimer's and Parkinson's disease. In recent years, interest has grown in the use of exosomes as a potential drug delivery system for various diseases and injuries. Importantly, exosomes originating from a patient's own cells exhibit minimal immunogenicity and possess remarkable stability along with inherent and adjustable targeting capabilities. This review explores the roles of exosomes in angiogenesis, lymphangiogenesis, and nerve repair with a specific emphasis on these processes within the cornea. Furthermore, it examines exosomes derived from specific cell types, discusses the advantages of exosome-based therapies in modulating these processes, and presents some of the most established methods for exosome isolation. Exosome-based treatments are emerging as potential minimally invasive and non-immunogenic therapies that modulate corneal angiogenesis and lymphangiogenesis, as well as enhance and accelerate endogenous corneal nerve repair.

DOI: https://doi.org/10.1016/j.jtos.2024.10.005
J Cell Mol Med. 2024 Oct;28(20): e70139

Unveiling exosomes: Cutting-edge isolation techniques and their therapeutic potential.

Farnaz Sani, Faezeh Shafiei, Farshad Dehghani, Yasaman Mohammadi, Mohammadhossein Khorraminejad-Shirazi, Abbas Fazel Anvari-Yazdi, Zahra Moayedfard, Negar Azarpira, Mahsa Sani.

  Exosomes are one type of nanosized membrane vesicles with an endocytic origin. They are secreted by almost all cell types and play diverse functional roles. It is essential for research purposes to differentiate exosomes from microvesicles and isolate them from other components in a fluid sample or cell culture medium. Exosomes are important mediators in cell-cell communication. They deliver their cargos, such as mRNA transcripts, microRNA, lipids, cytosolic and membrane proteins and enzymes, to target cells with or without physical connections between cells. They are highly heterogeneous in size, and their biological functions can vary depending on the cell type, their ability to interact with recipient cells and transport their contents, and the environment in which they are produced. This review summarized the recent progress in exosome isolation and characterization techniques. Moreover, we review the therapeutic approaches, biological functions of exosomes in disease progression, tumour metastasis regulation, immune regulation and some ongoing clinical trials.

Keywords:  cancer therapy; characterization; exosome; immune modulation; isolation

DOI:  https://doi.org/10.1111/jcmm.70139
Pain Rep. 2024 Dec;9(6): e1198

miRNA packaging into small extracellular vesicles and implications in pain.

Jason T DaCunza, Jason R Wickman, Seena K Ajit.

  Extracellular vesicles (EVs) are a heterogenous group of lipid bilayer bound particles naturally released by cells. These vesicles are classified based on their biogenesis pathway and diameter. The overlap in size of exosomes generated from the exosomal pathway and macrovesicles that are pinched off from the surface of the plasma membrane makes it challenging to isolate pure populations. Hence, isolated vesicles that are less than 200 nm are called small extracellular vesicles (sEVs). Extracellular vesicles transport a variety of cargo molecules, and multiple mechanisms govern the packaging of cargo into sEVs. Here, we discuss the current understanding of how miRNAs are targeted into sEVs, including the role of RNA binding proteins and EXOmotif sequences present in miRNAs in sEV loading. Several studies in human pain disorders and rodent models of pain have reported alterations in sEV cargo, including miRNAs. The sorting mechanisms and target regulation of miR-939, a miRNA altered in individuals with complex regional pain syndrome, is discussed in the context of inflammation. We also provide a broad overview of the therapeutic strategies being pursued to utilize sEVs in the clinic and the work needed to further our understanding of EVs to successfully deploy sEVs as a pain therapeutic.

Keywords:  Exosomes; Pain; Small extracellular vesicles; miR-939; miRNA; sEV biogenesis

DOI:  https://doi.org/10.1097/PR9.0000000000001198
J Nanobiotechnology. 2024 Oct 24. 22(1): 654

m6A-modified exosome-derived circHIF1α binding to KH domain of IGF2BP3 mediates DNA damage and arrests G1/S transition phase to resists bacterial infection in bacteremia.

Jiang Yu, Yidan Gao, Fei Liu, Yuyu Zhang, Jianda Li, Luogang Ding, Sufang Ren, Jie Yang, Jian Jiao, Gong Feng, Zhi Chen, Wenbo Sun, Jiaqiang Wu.

   BACKGROUND: Animal and human health are seriously threatened by bacterial infections, which can lead to bacteremia and extremely high rates of morbidity and mortality. Recently, there have been reports indicating the involvement of exosomal circular RNAs (circRNAs) in a range of human disorders and tumor types. However, the role of exosomal circRNAs in bacterial infection remains elusive.
METHODS: We extracted and identified exosomes from the culture medium of PIEC cells infected with or without Glaesserella parasuis. RNA sequencing analysis was performed on the exosomes to screen and identify circRNAs (circHIF1α) associated with Glaesserella parasuis infection. PIEC cells were infected with Staphylococcus aureus or Streptococcus suis 2 to further determine whether exosome-derived circHIF1α was the crucial circHIF1α associated with bacterial infections. The transmission process of exosomes and their circHIF1α between cells was clarified via exosome tracing and co-culture assay. Moreover, the mechanism of circHIF1α being packaged into exosomes was explored, and the effects of exosomes and their circHIF1α on cell proliferation, DNA damage and cell cycle were analyzed. In addition, the binding mode and site of interacting proteins with circHIF1α were further determined. In vivo and in vitro, the role of exosomes and their circHIF1α in host resistance to bacterial infection was confirmed.
RESULTS: We first discovered a new circHIF1α that was very stable and detectable, encapsulated into exosomes by hnRNPA2B1, and whose expression in exosomes of bacterially infected PIEC cells significantly decreased. Additionally, exosomal circHIF1α reduced bacterial infection both in vitro and in vivo and suppressed the growth of reception cells. Mechanistically, the circHIF1α interacted with the KH domain of IGF2BP3 in an m6A-modified manner, which mediated DNA damage to arrest the cells at the G1/S phase through the interaction between the regulator of Chromosome Condensation 2 (RCC2) and γ-H2AX protein. Exosomal circHIF1α is a unique therapeutic target for bacterial infection since this work highlights its critical function in fighting bacterial infection.

Keywords:  Bacterial infection; Cell cycle; DNA damage; Exosomal circHIF1α; IGF2BP3; m6A methylation

DOI:  https://doi.org/10.1186/s12951-024-02932-4
ACS Appl Mater Interfaces. 2024 Oct 22.

Ultrasound-Driven Nanomachine for Enhanced Sonodynamic Therapy of Non-Small-Cell Lung Cancer.

Wei Ping, Xiaoxin Zhang, Hao Zeng, Taomin Zhu, Ni Zhang, Qi Yan.

  Non-small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer, and there is an urgent need for developing novel therapies. Sonodynamic therapy exhibits exceptional tissue penetration and minimal harm to healthy tissue, making it extremely promising for cancer treatment. The efficacy of SDT is limited by the intricate immunological microenvironment and the resistance to tumor treatment. This study developed targeted nanoparticles that use ultrasound to concentrate on treating NSCLC. The hybrid targeted nanoparticles utilize gold nanoparticles as their fundamental component, with the outside modified with engineered macrophage exosomes and the aptamer S11e to specifically target NSCLC. Ultrasound could effectively eliminate tumors in NSCLC cells by destroying lysosomes via targeted nanoparticles. Simultaneously, fragmented tumor antigens could effectively activate dendritic cell cells to recruit T cells. This method has significant efficacy in suppressing the development of NSCLC and exhibits potential for therapeutic application.

Keywords:  dendritic cells; gold nanoparticle; lung cancer; sonodynamic therapy; ultrasound

DOI:  https://doi.org/10.1021/acsami.4c11546
J Obstet Gynaecol Res. 2024 Oct 21.

Research progress of exosomes in pathogenesis and treatment of preeclampsia.

Yue Xing, Luyao Kang, Lu Chen, Youyou Li, Dan Lu.

   AIM: Preeclampsia (PE) is a critical and severe disease in obstetrics, which seriously affects maternal and neonatal life safety and long-term prognosis. However, the etiology and pathogenesis of PE are complex, and no unified conclusion has been reached. The types and number of exosomes and their transport substances in PE patients changed. The study of exosomes in PE patients helps clarify the etiology, diagnosis, effective treatment, accurate monitoring, and prognosis.
METHOD: The published articles were reviewed.
RESULTS: Exosomes may affect endothelial and vascular production and function, participate in maternal-fetal immune regulation, and transport substances such as miRNAs, lncRNAs, and proteins involved in the development of PE. Detection of the contents of exosomes can help in the early diagnosis of PE, and can help to improve PE by inhibiting the action of exosomes or preventing their binding to target organs.
CONCLUSION: Exosomes may be involved in the development of PE, and exosomes can be used as markers for predicting the onset of PE and tracking the disease process and determining the prognosis, and exosomes have great potential in the treatment of PE.

Keywords:  diagnoses and treatment; exosomes; pathogenesis; preeclampsia

DOI:  https://doi.org/10.1111/jog.16106