bims-exocan 2022-11-13 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2022–11–13
eight papers selected by
Muhammad Rizwan, COMSATS University

Exosomes as Anticancer Drug Delivery Vehicles: Prospects and Challenges.
Recent Advances in Exosomal miRNA Biosensing for Liquid Biopsy.
Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives.
Optimization of a method for the clinical detection of serum exosomal miR-940 as a potential biomarker of breast cancer.
Emerging roles of mesenchymal stem cell-derived exosomes in gastrointestinal cancers.
Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics.
In situ detection of exosomal RNAs for cancer diagnosis.
Exosome Secretion and Epithelial-Mesenchymal Transition in Ovarian Cancer Are Regulated by Phospholipase D.

Front Biosci (Landmark Ed). 2022 Oct 27. 27(10): 293

Exosomes as Anticancer Drug Delivery Vehicles: Prospects and Challenges.

Yubo Zhang, Jian Li, Wei Gao, Na Xie.

  Exosomes, a subset of extracellular vesicles, are widely present in various body fluids and are involved in mediating intercellular communication. They have received extensive attention as diagnostic markers. The excellent physicochemical and biological properties of exosomes make them great potential drug delivery vehicles for the treatment of cancer and other diseases. However, various challenges need to be addressed for the clinical application of exosomes. This review introduces the biogenesis and uptake of exosomes and compares different approaches for isolation and drug loading, focusing on the application and current challenges of exosomes as drug delivery vehicles in cancer therapy.

Keywords:  cancer; drug delivery; exosomes

DOI:  https://doi.org/10.31083/j.fbl2710293
Molecules. 2022 Oct 22. pii: 7145. [Epub ahead of print]27(21):

Recent Advances in Exosomal miRNA Biosensing for Liquid Biopsy.

Bingqian Lin, Jinting Jiang, Jingxuan Jia, Xiang Zhou.

  As a noninvasive detection technique, liquid biopsy plays a valuable role in cancer diagnosis, disease monitoring, and prognostic assessment. In liquid biopsies, exosomes are considered among the potential biomarkers because they are important bioinformation carriers for intercellular communication. Exosomes transport miRNAs and, thus, play an important role in the regulation of cell growth and function; therefore, detection of cancer cell-derived exosomal miRNAs (exo-miRNAs) gives effective information in liquid biopsy. The development of sensitive, convenient, and reliable exo-miRNA assays will provide new perspectives for medical diagnosis. This review presents different designs and detection strategies of recent exo-miRNA assays in terms of signal transduction and amplification, as well as signal detection. In addition, this review outlines the current attempts at bioassay methods in liquid biopsies. Lastly, the challenges and prospects of exosome bioassays are also considered.

Keywords:  biosensing; exosomal miRNA; liquid biopsy

DOI:  https://doi.org/10.3390/molecules27217145
Molecules. 2022 Oct 27. pii: 7289. [Epub ahead of print]27(21):

Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives.

Amarjitsing Rajput, Akansh Varshney, Rashi Bajaj, Varsha Pokharkar.

  Currently, particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30-100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility with living tissues, low toxicity, extended blood circulation, capability to pass contents from one cell to another, non-immunogenic and special targeting of various cells, making them an excellent therapeutic carrier. Exosome-based molecules for drug delivery are still in the early stages of research and clinical trials. The problems and clinical transition issues related to exosome-based drugs need to be overcome using advanced tools for better understanding and systemic evaluation of exosomes. In this current review, we summarize the most up-to-date knowledge about the complex biological journey of exosomes from biogenesis and secretion, isolation techniques, characterization, loading methods, pharmaceutical and therapeutic applications, challenges and future perspectives of exosomes.

Keywords:  biogenesis; drug delivery; exosomes; isolation; therapeutic applications

DOI:  https://doi.org/10.3390/molecules27217289
Front Oncol. 2022 ;12 956167

Optimization of a method for the clinical detection of serum exosomal miR-940 as a potential biomarker of breast cancer.

Zhiyun Gu, Haojie Yin, Haiwei Zhang, Hui Zhang, Xiaoyu Liu, Xiaohua Zeng, Xiaodong Zheng.

  Serum exosomal microRNAs (miRNAs) are potential biomarkers for tumor diagnosis. Clinically, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) can be used to determine the expression of exosomal miRNAs in the serum of breast cancer patients. The prerequisites for obtaining meaningful serum exosomal miRNA data of breast cancer patients include a suitable extraction method for exosomes and RT-qPCR data standardized by internal reference genes. However, the appropriate methods for the extraction of exosomes and the applicability of reference genes for analyzing exosomal miRNAs in breast cancer patients remain to be studied. This study compared the effects of three exosome extraction methods as well as the expression of exosomal miRNA in different initial serum amounts and at different serum states to identify the selection of the best method for serum exosome extraction. Five candidate reference genes including miR-16, miR-484, miR-1228, miR-191 and miR-423 for standardizing serum exosomal miRNAs were screened using five algorithms and were used for the quantification of serum exosomal miR-940. Significant downregulation of serum exosomal miR-940 expression in breast cancer was detected using miR-191 and miR-1228, whereas no significant down or up regulation was observed with miR-484, miR-423 and miR-16. Previous studies have shown that the expression level of miR-940 is downregulated in breast cancer tissues. The absolute quantitative results showed that miR-940 was significantly downregulated in breast cancer serum exosomes, which was consistent with the results from the analysis using miR-191 or miR-1228 as reference genes. Therefore, miR-191 and miR-1228 could serve as reference genes for the relative quantification of serum exosomal miRNAs. This finding indicated the importance of rigorously evaluating the stability of reference genes and standardization for serum exosomal miRNA expression. Moreover, the level of serum exosomal miR-940 in breast cancer could reflect the presence of lymph node metastasis and the status of HER2/neu, which indicates its potential as a biomarker for breast cancer metastasis. In summary, an optimized protocol for the detection of serum exosomal miR-940 as a breast cancer marker was preliminarily established.

Keywords:  RT-qPCR; breast cancer; exosomes; miR-940; reference genes

DOI:  https://doi.org/10.3389/fonc.2022.956167
Front Bioeng Biotechnol. 2022 ;10 1019459

Emerging roles of mesenchymal stem cell-derived exosomes in gastrointestinal cancers.

Naijian Wang, Bing Pei, Xinyi Yuan, Chengxue Yi, Dickson Kofi Wiredu Ocansey, Hua Qian, Fei Mao.

  Gastrointestinal tumours are the most common solid tumours, with a poor prognosis and remain a major challenge in cancer treatment. Mesenchymal stem cells (MSC) are multipotent stromal cells with the potential to differentiate into multiple cell types. Several studies have shown that MSC-derived exosomes have become essential regulators of intercellular communication in a variety of physiological and pathological processes. Notably, MSC-derived exosomes support or inhibit tumour progression in different cancers through the delivery of proteins, RNA, DNA, and bioactive lipids. Herein, we summarise current advances in MSC-derived exosomes in cancer research, with particular reference to their role in gastrointestinal tumour development. MSC-derived exosomes are expected to be a novel potential strategy for the treatment of gastrointestinal cancers.

Keywords:  drug carrier; exosome; gastrointestinal cancer; mesenchymal stem cell; miRNA

DOI:  https://doi.org/10.3389/fbioe.2022.1019459
ACS Nano. 2022 Nov 10.

Exosomes─Nature's Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics.

Rumiana Tenchov, Janet M Sasso, Xinmei Wang, Wen-Shing Liaw, Chun-An Chen, Qiongqiong Angela Zhou.

  Exosomes are a subgroup of nanosized extracellular vesicles enclosed by a lipid bilayer membrane and secreted by most eukaryotic cells. They represent a route of intercellular communication and participate in a wide variety of physiological and pathological processes. The biological roles of exosomes rely on their bioactive cargos, including proteins, nucleic acids, and lipids, which are delivered to target cells. Their distinctive properties─innate stability, low immunogenicity, biocompatibility, and good biomembrane penetration capacity─allow them to function as superior natural nanocarriers for efficient drug delivery. Another notably favorable clinical application of exosomes is in diagnostics. They hold various biomolecules from host cells, which are indicative of pathophysiological conditions; therefore, they are considered vital for biomarker discovery in clinical diagnostics. Here, we use data from the CAS Content Collection and provide a landscape overview of the current state and delineate trends in research advancement on exosome applications in therapeutics and diagnostics across time, geography, composition, cargo loading, and development pipelines. We discuss exosome composition and pathway, from their biogenesis and secretion from host cells to recipient cell uptake. We assess methods for exosome isolation and purification, their clinical applications in therapy and diagnostics, their development pipelines, the exploration goals of the companies, the assortment of diseases they aim to treat, development stages of their research, and publication trends. We hope this review will be useful for understanding the current knowledge in the field of medical applications of exosomes, in an effort to further solve the remaining challenges in fulfilling their potential.

Keywords:  biomarker; blood−brain barrier; diagnostics; drug delivery; exosome; extracellular vesicle; nanocarrier; nanoparticle; therapeutics

DOI:  https://doi.org/10.1021/acsnano.2c08774
Acta Biomater. 2022 Nov 04. pii: S1742-7061(22)00724-3. [Epub ahead of print]

In situ detection of exosomal RNAs for cancer diagnosis.

Zhiwei Sun, Yanqiu Wu, Fucheng Gao, Hui Li, Chuanxin Wang, Lutao Du, Lun Dong, Yanyan Jiang.

  Exosomes are considered as biomarkers reflecting the physiological state of the human body. Studies have revealed that the expression levels of specific exosomal RNAs are closely associated with certain cancers. Thus, detection of exosomal RNA offers a new avenue for liquid biopsy of cancers. Many exosomal RNA detection methods based on various principles have been developed, and most of the methods detect the extracted RNAs after lysing exosomes. Besides complex and time-consuming extraction steps, a major drawback of this approach is the degradation of the extracted RNAs in the absence of plasma membrane and cytosol. In addition, there is considerable loss of RNAs during their extraction. In situ detection of exosomal RNAs can avoid these drawbacks, thus allowing higher diagnostic reliability. In this paper, in situ detection of exosomal RNAs was systematically reviewed from the perspectives of detection methods, transport methods of the probe systems, probe structures, signal amplification strategies, and involved functional materials. Furthermore, the limitations and possible improvements of the current in situ detection methods for exosomal RNAs towards the clinical diagnostic application are discussed. This review aims to provide a valuable reference for the development of in situ exosomal RNA detection strategies for non-invasive diagnosis of cancers. STATEMENT OF SIGNIFICANCE: Certain RNAs have been identified as valuable biomarkers for some cancers, and sensitive detection of cancer-related RNAs is expected to achieve better diagnostic efficacy. Currently, the detection of exosomal RNAs is receiving increasing attention due to their high stability and significant concentration differences between patients and healthy individuals. In situ detection of exosomal RNAs has greater diagnostic reliability due to the avoidance of RNA degradation and loss. However, this mode is still limited by some factors such as detection methods, transport methods of the probe systems, probe structures, signal amplification strategies, etc. This review focuses on the progress of in situ detection of exosomal RNAs and aims to promote the development of this field.

Keywords:  cancer diagnosis; exosomal RNAs; in situ detection; probe structures; signal amplification; transport methods

DOI:  https://doi.org/10.1016/j.actbio.2022.10.061
Int J Mol Sci. 2022 Oct 31. pii: 13286. [Epub ahead of print]23(21):

Exosome Secretion and Epithelial-Mesenchymal Transition in Ovarian Cancer Are Regulated by Phospholipase D.

Hadil Onallah, Sheethal Thomas Mannully, Ben Davidson, Reuven Reich.

  Phospholipase D (PLD) isoenzymes participate in a variety of cellular functions that are mostly attributed to phosphatidic acid (PA) synthesis. Dysregulation of PLD regulates tumor progression and metastasis, yet little is known about the underlying mechanism. We previously reported on the expression and clinical role of the PLD isoenzymes PLD1 and PLD2 in tubo-ovarian high-grade serous carcinoma (HGSC). In the present study, we investigated the biological function of PLD1 and PLD2 using the OVCAR-3 and OVCAR-8 HGSC cell lines. KO cell lines for both PLDs were generated using CRISPR/CAS9 technology and assayed for exosome secretion, spheroid formation, migration, invasion and expression of molecules involved in epithelial-mesenchymal transition (EMT) and intracellular signaling. Significant differences between PLD1 and PLD2 KO cells and controls were observed for all the above parameters, supporting an important role for PLD in regulating migration, invasion, metastasis and EMT.

Keywords:  Phospholipase D; epithelial-mesenchymal transition; exosomes; ovarian cancer

DOI:  https://doi.org/10.3390/ijms232113286