Advanced Nanoencapsulation-Enabled Ultrasensitive Analysis: Unraveling Tumor Extracellular Vesicle Subpopulations for Differential Diagnosis of Hepatocellular Carcinoma via DNA Cascade Reactions
作者全名：Li, Xinyu; Liu, Yuanjie; Fan, Yunpeng; Tian, Gang; Shen, Bo; Zhang, Songzhi; Fu, Xuhuai; He, Wen; Tao, Xingyu; Ding, Xiaojuan; Li, Xinmin; Ding, Shijia
作者地址：[Li, Xinyu; Liu, Yuanjie; Fan, Yunpeng; Zhang, Songzhi; He, Wen; Tao, Xingyu; Ding, Shijia] Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Minist Educ, Chongqing 400016, Peoples R China; [Fan, Yunpeng; Shen, Bo; Li, Xinmin] Chongqing Hosp Tradit Chinese Med, Dept Lab Med, Chongqing Key Lab Sichuan Chongqing Coconstruct Di, Chongqing 400016, Peoples R China; [Tian, Gang] Southwest Med Univ, Affiliated Hosp, Sichuan Prov Engn Technol Res Ctr Mol Diag Clin Di, Dept Lab Med,Mol Diag Clin Dis Key Lab Luzhou, Luzhou 646000, Sichuan, Peoples R China; [Fu, Xuhuai] Chongqing Univ, Canc Hosp, Dept Clin Lab, Chongqing Key Lab Translat Res Canc Metastasis & I, Chongqing 400030, Peoples R China; [Fu, Xuhuai] Chongqing Canc Inst, Chongqing 400030, Peoples R China; [Ding, Xiaojuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing 400016, Peoples R China
通信作者：Ding, SJ (通讯作者)，Chongqing Med Univ, Coll Lab Med, Key Lab Clin Lab Diagnost, Minist Educ, Chongqing 400016, Peoples R China.; Li, XM (通讯作者)，Chongqing Hosp Tradit Chinese Med, Dept Lab Med, Chongqing Key Lab Sichuan Chongqing Coconstruct Di, Chongqing 400016, Peoples R China.; Ding, XJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Lab Med, Chongqing 400016, Peoples R China.
来源：ACS NANO
ESI学科分类：MATERIALS SCIENCE
WOS号：WOS:001204965000001
JCR分区：Q1
影响因子：15.8
年份：2024
卷号：18
期号：17
开始页：11389
结束页：11403
文献类型：Article
关键词：tumor-derived extracellular vesicles; DNA-assisted individualEV nanoencapsulation; selective packaging; machinelearning; hepatocellular carcinoma; differentialdiagnosis; flow cytometry analysis
摘要：Tumor-derived extracellular vesicles (tEVs) hold immense promise as potential biomarkers for the precise diagnosis of hepatocellular carcinoma (HCC). However, their clinical translation is hampered by their inherent characteristics, such as small size and high heterogeneity and complex environment, including non-EV particles and normal cell-derived EVs, which prolong separation procedures and compromise detection accuracy. In this study, we devised a DNA cascade reaction-triggered individual EV nanoencapsulation (DCR-IEVN) strategy to achieve the ultrasensitive and specific detection of tEV subpopulations via routine flow cytometry in a one-pot, one-step fashion. DCR-IEVN enables the direct and selective packaging of multiple tEV subpopulations in clinical serum samples into flower-like particles exceeding 600 nm. This approach bypasses the need for EV isolation, effectively reducing interference from non-EV particles and nontumor EVs. Compared with conventional analytical technologies, DCR-IEVN exhibits superior efficacy in diagnosing HCC owing to its high selectivity for tEVs. Integration of machine learning algorithms with DCR-IEVN resulted in differential diagnosis accuracy of 96.7% for the training cohort (n = 120) and 93.3% for the validation cohort (n = 30), effectively distinguishing HCC, cirrhosis, and healthy donors. This strategy offers a streamlined workflow and rapid assay completion and requires only small-volume serum samples and routine clinical devices, facilitating the clinical translation of tEV-based tumor diagnosis.
基金机构：National Natural Science Foundation of China [82272432, 82202649]; Chongqing Talent-Innovation Leader Project [CQYC20210302385]; Natural Science Foundation of Chongqing, China [cstc2021jcyj-msxmX0325, CSTB2023NSCQ-MSX0897, CSTB2022NSCQ-MSX0377]; China Postdoctoral Science Foundation [2023MD744144]; Joint Project of Chongqing Health Commission and Science and Technology Bureau [2022MSXM008, 2022MSXM106, 2023QNXM026, 2023QNXM028]; Special Funding for Postdoctoral Research Projects in Chongqing [2022CQBSHTB2028]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [kryc-yq-2125]
基金资助正文：This work was funded by the financial support from the National Natural Science Foundation of China (82272432, 82202649), the Chongqing Talent-Innovation Leader Project (CQYC20210302385), the Natural Science Foundation of Chongqing, China (cstc2021jcyj-msxmX0325, CSTB2023NSCQ-MSX0897, CSTB2022NSCQ-MSX0377),China Postdoctoral Science Foundation (2023MD744144), Joint Project of Chongqing Health Commission and Science and Technology Bureau (2022MSXM008,2022MSXM106, 2023QNXM026, and 2023QNXM028), Special Funding for Postdoctoral Research Projects in Chongqing (2022CQBSHTB2028), and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (kryc-yq-2125).
