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      Ratiometric electrochemical OR gate assay for NSCLC-derived exosomes

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          Abstract

          Non-small cell lung cancer (NSCLC) is the most common pathological type of LC and ranks as the leading cause of cancer deaths. Circulating exosomes have emerged as a valuable biomarker for the diagnosis of NSCLC, while the performance of current electrochemical assays for exosome detection is constrained by unsatisfactory sensitivity and specificity. Here we integrated a ratiometric biosensor with an OR logic gate to form an assay for surface protein profiling of exosomes from clinical serum samples. By using the specific aptamers for recognition of clinically validated biomarkers (EpCAM and CEA), the assay enabled ultrasensitive detection of trace levels of NSCLC-derived exosomes in complex serum samples (15.1 particles μL −1 within a linear range of 10 2–10 8 particles μL −1). The assay outperformed the analysis of six serum biomarkers for the accurate diagnosis, staging, and prognosis of NSCLC, displaying a diagnostic sensitivity of 93.3% even at an early stage (Stage I). The assay provides an advanced tool for exosome quantification and facilitates exosome-based liquid biopsies for cancer management in clinics.

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          Supplementary Information

          The online version contains supplementary material available at 10.1186/s12951-023-01833-2.

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          Most cited references77

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            The biology, function, and biomedical applications of exosomes

            The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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              Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

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                Author and article information

                Contributors
                yyc2166@sjtu.edu.cn
                jiayi.wang@sjtu.edu.cn
                linhuang@shsmu.edu.cn
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                24 March 2023
                24 March 2023
                2023
                : 21
                : 104
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, 200030 China
                [2 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, 200030 China
                [3 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, State Key Laboratory for Oncogenes and Related Genes, School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, , Shanghai Jiao Tong University, ; Shanghai, 200030 China
                Article
                1833
                10.1186/s12951-023-01833-2
                10037838
                36964516
                87a87a6f-4847-4fc8-9797-b100b7b6a3bf
                © The Author(s) 2023

                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
                : 7 December 2022
                : 27 February 2023
                Funding
                Funded by: Innovative Research Team of High-level Local Universities in Shanghai
                Award ID: SHSMU-ZLCX20212302
                Award ID: SHSMU-ZLCX20212302
                Award Recipient :
                Funded by: Shanghai Sailing Program
                Award ID: 20YF1434400 and 21YF1443000
                Award ID: 20YF1434400 and 21YF1443000
                Award Recipient :
                Funded by: National Natural Science Foundation of China
                Award ID: 81971771
                Award ID: 82001985
                Award Recipient :
                Funded by: Shanghai Institutions of Higher Learning
                Award ID: 2021-01-07-00-02-E00083
                Award Recipient :
                Funded by: Innovation Group Project of Shanghai Municipal Health Commission
                Award ID: 2019CXJQ03
                Award Recipient :
                Funded by: Innovation Research Plan by the Shanghai Municipal Education Commission
                Award ID: ZXWF082101
                Award Recipient :
                Funded by: National Research Center for Translational Medicine Shanghai
                Award ID: TMSK-2021-124, NRCTM(SH)-2021-06
                Award Recipient :
                Funded by: Medical-Engineering Joint Funds of Shanghai Jiao Tong University
                Award ID: YG2019QNA44, YG2021ZD09, YG2022QN107
                Award Recipient :
                Funded by: Shanghai Science and Technology Commission
                Award ID: 20ZR1440000
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2023

                Biotechnology
                ratiometric biosensor,or logic gate,exosomes,non-small cell lung cancer,clinical diagnostics

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