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      Recent advances in exosome-mediated nucleic acid delivery for cancer therapy

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          Abstract

          Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs.

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          Cancer Statistics, 2021

          Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
          Article 0 comments Cited 6814 times – based on 0 reviews     Review now
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            Cancer statistics, 2018

            Kimberly D Miller, Rebecca Siegel, Ahmedin Jemal (2018)
            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
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              Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

              Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)
              Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
              Article 0 comments Cited 2281 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jia Liu: liujia870702@126.com
                Chengbin Yang: cbyang@szu.edu.cn
                Journal
                Journal ID (nlm-ta): J Nanobiotechnology
                Journal ID (iso-abbrev): J Nanobiotechnology
                Title: Journal of Nanobiotechnology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-3155
                Publication date (Electronic): 14 June 2022
                Publication date PMC-release: 14 June 2022
                Publication date Collection: 2022
                Volume: 20
                Electronic Location Identifier: 279
                Affiliations
                [1 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Central Laboratory of Longgang District People’s Hospital of Shenzhen & The Second Affiliated Hospital, , The Chinese University of Hong Kong, ; Shenzhen, 518172 China
                [2 ]GRID grid.263488.3, ISNI 0000 0001 0472 9649, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, , Shenzhen University, ; Shenzhen, 518060 China
                Article
                Publisher ID: 1472
                DOI: 10.1186/s12951-022-01472-z
                PMC ID: 9194774
                PubMed ID: 35701788
                SO-VID: 51f011e8-79dc-45f4-a634-0356758532dc
                Copyright © © The Author(s) 2022
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 14 March 2022
                Date accepted : 19 May 2022
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: 81900264
                Award Recipient :
                Funded by: Natural Science Foundation of Guangdong Province
                Award ID: 2021A1515012159
                Award ID: 2019A1515012163
                Award Recipient :
                Funded by: the Shenzhen Science and Technology Innovation Fund
                Award ID: JCYJ20210324130609027
                Award Recipient :
                Funded by: the Project of Administration of Traditional Chinese Medicine Guangdong Province
                Award ID: 20211347
                Award Recipient :
                Funded by: the Longgang Medical and Health Science and Technology Project
                Award ID: LGKCYLWS2020040
                Award Recipient :
                Funded by: Guangdong MedicalScience and Technology Research Funding
                Award ID: A2019359
                Award Recipient :
                Funded by: University Stable Support Research Funding of Shenzhen
                Award ID: 20200813153346001
                Award Recipient :
                Funded by: SZU Top Ranking Project
                Award ID: 86000000210
                Award Recipient :
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2022

                ScienceOpen disciplines: Biotechnology
                Keywords: gene therapy,exosome,nucleic acid drug,delivery,cancer treatment
                Data availability:
                ScienceOpen disciplines: Biotechnology
                Keywords: gene therapy, exosome, nucleic acid drug, delivery, cancer treatment

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