bims-exocan 2023-04-23 papers

Issue of 2023–04–23
six papers selected by
Muhammad Rizwan, COMSATS University

Cancer Med. 2023 Apr 20.

Hypoxic lung adenocarcinoma-derived exosomal miR-1290 induces M2 macrophage polarization by targeting SOCS3.

Jiahui Gu, Shengrui Yang, Xueying Wang, Yining Wu, Jia Wei, Jian Xu.

BACKGROUND: Exosomes are critical mediators of tumor cell-microenvironment cross talk. However, the mechanisms by which hypoxic Lung adenocarcinoma (LUAD)-derived exosomes modulate macrophage polarization remain largely unknown. The aim of this study was to investigate the effects of hypoxic LUAD-derived exosome on macrophage polarization and explore the underlying molecular mechanism.
MATERIALS AND METHODS: LUAD-derived exosomes were isolated, and then confirmed by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Internalization of exosomes in macrophages was detected by confocal microscope. Gain- and loss-of-function experiments, rescue experiments, and xenograft models were performed to uncover the underlying mechanisms of exosomal miR-1290 induced macrophage polarization in vitro and in vivo.
RESULTS: miR-1290 was enriched in hypoxic LUAD cancer cell-derived exosomes and could be transferred to macrophages. Overexpression of miR-1290 in macrophages-induced polarization of M2 phenotype. Luciferase assay verified SOCS3 was the target of miR-1290. Hypoxic LUAD cell-derived exosomal miR-1290 activated the STAT3 signaling pathway by targeting SOCS3 to promote M2 macrophage polarization.
CONCLUSION: Hypoxic LUAD cells generate miR-1290-rich exosomes that promote M2 polarization of macrophages. Targeting exosomal miR-1290 may provide a potential immunotherapeutic strategy for LUAD.

Keywords: exosome; hypoxia; lung adenocarcinoma; macrophage polarization; miR-1290

DOI: https://doi.org/10.1002/cam4.5954

Int J Nanomedicine. 2023 ;18 1989-2001

Serum Exosome-Derived piRNAs Could Be Promising Biomarkers for HCC Diagnosis.

Tao Rui, Kai Wang, Aizhai Xiang, Jufeng Guo, Ning Tang, Xin Jin, Yimou Lin, Jian Liu, Xiaobing Zhang.

Background: Serum exosome-based liquid biopsy has significant advantages for screening and diagnosing hepatocellular carcinoma (HCC). P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel small silencing RNAs that have been identified to function in cancer-related signalling pathways. However, studies on the presence of piRNAs in serum exosomes from HCC patients and their diagnostic values in HCC are not well reported. Our aim is to validate serum exosome-derived piRNAs as the valuable component of liquid biopsy for diagnosing HCC.
Methods: We used small RNA (sRNA) sequencing to profile piRNAs from serum exosomes and describe the base distribution characteristics of serum exosome-derived piRNAs. Serum exosomes from 125 HCC patients and 44 nontumor donors were included in this study.
Results: We found that piRNAs were components of serum exosomes from HCC patients. A total of 253 differentially expressed serum exosome-derived piRNAs were screened from HCC compared with the piRNAs from nontumor donors. Serum exosome-derived piRNAs from HCC displayed a distinctive base distribution. To further confirm the potential diagnostic value of serum exosome-derived piRNAs in HCC, we detected the levels of the top 5 upregulated piRNAs in our Chinese cohort. The training set and validation set both showed that all 5 piRNAs were dramatically increased in the serum exosomes from HCC compared with the piRNAs from non-tumour donors. The piRNAs could strongly identify HCC patients from non-tumour donors according to the area under the receiver operating characteristic (AUROC) model. Additionally, the piRNAs could also present significant values for the diagnosis of HCC with low tumour burden.
Conclusion: piRNAs enriched the components of serum exosomes from HCC and could serve as promising biomarkers for HCC diagnosis.

Keywords: HCC; biomarker; exosome; piRNA; sRNA-seq

DOI: https://doi.org/10.2147/IJN.S398462

Appl Biochem Biotechnol. 2023 Apr 17.

Leukemia-derived Exosomes Can Induce Responses Related to Tumorigenesis on Non-tumoral Astrocytes.

Parisa Zamani Esmati, Javad Baharara, Sajad Sahab-Negah, Khadijeh Nejad Shahrokhabadi.

Cancer is the second cause of disability and death worldwide. Identifying communication between cancer cells and normal cells can shed light on the underlying metastatic mechanisms. Among different suspected mechanisms, exosomes derived from cancer cells have been introduced as a main key player in metastatic processes. To this point, we evaluated the effects of exosomes derived from the leukemia nalm6 cell line on astrocytes behavior, such as proliferation and inflammatory pathways. To assess astrocyte responses, data were obtained by MTT, Annexin/PI to indicate proliferation and apoptosis. Further analyses were performed by Real-time PCR and western blot to assess the expression of IL6, IL1β, NFkβ, TNFα, and aquaporin-4 (AQP4). Our results demonstrated that the proliferation of astrocytes was significantly increased when treated with exosomes derived from Nalm6 cells. We also found that the expression of IL6, IL1β, NFkβ, and TNFα were significantly increased at the mRNA level when exposed to exosomes derived from Nalm6 cells. Finally, the mRNA and protein levels of AQP4 were profoundly increased after being treated by exosomes derived from Nalm6 cells. To sum up, our data indicated that the secretion of cancer cells could induce responses related to tumorigenesis. However, further studies on this topic are warranted to clarify exosomes' role in metastasis.

Keywords: Acute lymphoblastic leukemia; Aquaporin-4; Astrocyte; Exosomes; Nalm6 cells

DOI: https://doi.org/10.1007/s12010-023-04428-7

Crit Rev Ther Drug Carrier Syst. 2023 ;40(4): 101-133

Exosomes: Recent Advances and Challenges as Targeted Therapeutic Delivery Vesicles.

Sourabh Jadhav, Ankaj Kumar, Arvind Gulbake.

The exosome is a naturally derived nanostructured lipid vesicle that ranges from 40-100 nm in size and is utilized to transport drugs, and biological macromolecules, including therapeutic RNA and proteins. It is a membrane vesicle actively released by cells to transport cellular components with a purpose for biological events. The conventional isolation technique has several drawbacks, including low integrity, low purity, long processing time, and sample preparation. Therefore, microfluidic technologies are more widely accepted for the isolation of pure exosomes, but due to cost and expertise requirements, this technology is also facing challenges. The bioconjugation of small and macro-molecules to the surface of exosomes is a very interesting and emerging approach for achieving the specific target, therapeutic purpose, in vivo imaging, and many more. Although emerging strategies resolve a few challenges, exosomes are still unexplored complex nano-vesicles with excellent properties. This review has briefly elaborated on contemporary isolation techniques and loading approaches. We have also discussed the surface-modified exosomes by different conjugation methods and their applications as targeted drug delivery vesicles. The challenges associated with the exosomes, patents, and clinical investigations are the main highlight of this review.

DOI: https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2022044495

Biochem Pharmacol. 2023 Apr 17. pii: S0006-2952(23)00146-6. [Epub ahead of print] 115555

Viral Vectors, Exosomes, and Vexosomes: Potential Armamentarium for Delivering CRISPR/Cas to Cancer Cells.

Mahdieh Farzanehpour, Ali Miri, Akbar Ghorbani Alvanegh, Hadi Esmaeili Gouvarchinghaleh.

The underlying cause of cancer is genetic disruption, so gene editing technologies, particularly CRISPR/Cas systems can be used to go against cancer. The field of gene therapy has undergone many transitions over its 40-year history. Despite its many successes, it has also suffered many failures in the battle against malignancies, causing really adverse effects instead of therapeutic outcomes. At the tip of this double-edged sword are viral and non-viral-based vectors, which have profoundly transformed the way scientists and clinicians develop therapeutic platforms. Viruses such as lentivirus, adenovirus, and adeno-associated viruses are the most common viral vectors used for delivering the CRISPR/Cas system into human cells. In addition, among non-viral vectors, exosomes, especially tumor-derived exosomes (TDEs), have proven to be quite effective at delivering this gene editing tool. The combined use of viral vectors and exosomes, called vexosomes, seems to be a solution to overcoming the obstacles of both delivery systems.

Keywords: CRISPR/Cas systems; Cancer therapy; Exosome; Vexosome; Viral vectors

DOI: https://doi.org/10.1016/j.bcp.2023.115555

Adv Sci (Weinh). 2023 Apr 20. e2300552

Engineering Extracellular Vesicles as Delivery Systems in Therapeutic Applications.

Liwei Wang, Di Wang, Zhaoming Ye, Jianbin Xu.

Extracellular vesicles (EVs) are transport vesicles secreted by living cells and released into the extracellular environment. Recent studies have shown that EVs serve as "messengers" in intercellular and inter-organismal communication, in both normal and pathological processes. EVs, as natural nanocarriers, can deliver bioactivators in therapy with their endogenous transport properties. This review article describes the engineering EVs of sources, isolation method, cargo loading, boosting approach, and adjustable targeting of EVs. Furthermore, the review summarizes the recent progress made in EV-based delivery systems applications, including cancer, cardiovascular diseases, liver, kidney, nervous system diseases, and COVID-19 and emphasizes the obstacles and challenges of EV-based therapies and possible strategies.

Keywords: drug delivery; extracellular vesicles; nanocarrier; targeted therapy

DOI: https://doi.org/10.1002/advs.202300552