bims-exocan 2023-09-24 papers

Issue of 2023–09–24
five papers selected by
Muhammad Rizwan, COMSATS University

Analyst. 2023 Sep 18.

Recent progress in quantitative technologies for the analysis of cancer-related exosome proteins.

Exosomes are a kind of extracellular vesicles, which play a significant role in intercellular communication and molecular exchange. Cancer-derived exosomes are potential and ideal biomarkers for the early diagnosis and treatment monitoring of cancers because of their abundant biological information and contribution to the interaction between cancer cells and the tumor microenvironment. However, there are a number of drawbacks, such as low sensitivity and tedious steps, in conventional detection techniques. Furthermore, exosome quantification is not enough to accurately distinguish cancer patients from healthy individuals. Therefore, developing efficient, accurate, and inexpensive exosome surface protein analysis techniques is necessary and critical. In recent years, a considerable number of researchers have presented novel detection strategies in this field. This review summarizes the recent progress in quantitative technologies for the analysis of cancer-related exosome proteins, mainly including the detection methods based on aptamers, nanomaterials, and antibodies, discusses a roadmap for future developments, and aims to offer an innovative perspective of exosome research.

DOI: https://doi.org/10.1039/d3an01228j

Chem Pharm Bull (Tokyo). 2023 Sep 21.

Exosome-hijacking drug delivery system with branched arginine linker effectively deliver antisense oligonucleotides into lung adenocarcinoma cells.

Shota Oyama, Mao Tomita, Moeka Hata, Yu Mikame, Tsuyoshi Yamamoto, Eishi Ashihara, Asako Yamayoshi.

Exosomes are a type of extracellular vesicles that contain diverse molecules and are present in our body fluids. They play a crucial role in transporting materials and transmitting signals between cells. Currently, there have been numerous reports on the use of exosomes in drug delivery systems (DDS). However, most existing methods for utilizing exosomes in DDS require the isolation and purification of exosomes, which raises concerns about yield and potential damage to the exosomes.Recently, we have developed a novel DDS called "ExomiR-Tracker" that harnesses exosomes without the need for isolation and purification. This system aims to deliver nucleic acid drugs effectively. ExomiR-Tracker consists of an anti-exosome antibody equipped with nona-D-arginines (9 mer) and nucleic acid drugs which have complementary sequence of target microRNA (anti-miR). In this study, we modified ExomiR-Tracker by incorporating branched nona-D-arginines (9 + 9 mer) molecules (referred to as Branch ExomiR-Tracker) and evaluated its efficacy in lung adenocarcinoma cells (A549 cells). The improved complex formation ability and enhanced cellular uptake of anti-miR, demonstrated by our findings, highlight the advantages of incorporating branched oligoarginine peptides into the ExomiR-Tracker platform. These results represent significant progress in revealing the effectiveness of Branch ExomiR-Tracker against adhesive cancer cells, which has not been shown to be effective with the conventional Linear ExomiR-Tracker.

Keywords: drug delivery system; exosome; nucleic acid drug

DOI: https://doi.org/10.1248/cpb.c23-00430

Biochem Genet. 2023 Sep 20.

Exosomal circKIAA1797 Regulates Cell Progression and Glycolysis by Targeting miR-4429/PBX3 Pathway in Gastric Cancer.

Xiaomei Zheng, Hongwei Xiao, Xiaoxiao Liu, Ting Huang, Chengwei Deng.

In recent years, circular RNAs (circRNAs) are extensively studied in the progression of various types of cancer, while the mechanism of circKIAA1797 is rarely studied in gastric cancer (GC). Hence, this research aimed to investigate the expression of exosomal circKIAA1797 and its biological function in GC cells. Exosomes were extracted from the serum of GC patients and identified by transmission electron microscopy (TEM) and nanoparticle tracking analyzer (NTA). CD81, CD63, Bcl-2, Bax, and pre-leukemia transcription factor 3 (PBX3) protein levels were detected using western blot assay. circKIAA1797, microRNA-4429 (miR-4429), and PBX3 mRNA were determined by quantitative real-time PCR (RT-qPCR). Cell proliferation, migration, invasion, and apoptosis were assessed using colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, and flow cytometry assay. Glucose consumption and lactate production levels were examined using glycolysis detection kits. The interaction between miR-4429 and circKIAA1797 or PBX3 was identified using dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay. Xenograft mouse model assay was used to investigate the effect of exosomal circKIAA1797 in vivo. It was found that circKIAA1797 was up-regulated in GC tissues and cells, as well as in the exosomes derived from the serum of GC patients. Silencing of exosomal circKIAA1797 could hamper cell progression and glycolytic metabolism of GC. Mechanically, circKIAA1797 acted as a sponge of miR-4429 to regulate PBX3 expression. Moreover, the knockdown of exosomal circKIAA1797 repressed tumor growth in vivo. Our data demonstrated that knockdown of exosomal circKIAA1797 suppressed GC malignant phenotypes by regulating miR-4429/PBX3 axis, which might offer a promising therapeutic strategy for GC treatment.

Keywords: Exosomal circKIAA1797; Gastric cancer; PBX3; miR-4429

DOI: https://doi.org/10.1007/s10528-023-10529-z

Curr Gene Ther. 2023 ;23(5): 330-342

Exosomal miRNAs as Next-generation Therapy Vehicles in Breast Cancer.

Priyanka Thakur, Harshita Dahiya, Ankur Kaushal, Vijai Kumar Gupta, Adesh K Saini, Reena V Saini.

The second most pervasive cancer affecting the survival of women across the world is breast cancer. One of the biggest challenges in breast cancer treatment is the chemoresistance of cancer cells to various medications after some time. Therefore, highly specific blood-based biomarkers are required for early breast cancer diagnosis to overcome chemoresistance and improve patient survival. These days, exosomal miRNAs have attracted much attention as early diagnostic blood-based biomarkers because of their high stability, secretion from malignant tumor cells, and excellent specificity for different breast cancer subtypes. In addition, exosomal miRNAs regulate cell proliferation, invasion, metastasis, and apoptosis by binding to the 3'UTR of their target genes and limiting their production. This review focuses on the functions of exosomal miRNAs in tumorigenesis via targeting multiple signaling pathways as well as chemosensitivity and resistance mechanisms. In addition, the growing pieces of evidence discussed in this review suggest that circulating exosomal miRNAs could be utilized as potential next-generation therapeutic target vehicles in the treatment of breast cancer.

Keywords: Exosomal miRNAs; breast cancer; chemoresistance; metastasis; target genes; therapeutic biomarkers

DOI: https://doi.org/10.2174/1566523223666230215103524

Cancer Lett. 2023 Sep 14. pii: S0304-3835(23)00345-2. [Epub ahead of print] 216394

Exosomes as emerging nanoplatform in cancer therapy.

Farrukh Aqil, Ramesh Gupta.

DOI: https://doi.org/10.1016/j.canlet.2023.216394