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通过整合硼酸酯亲和力和局部印迹后修饰来提高细胞印迹聚二甲基硅氧烷的性能,用于从癌症患者中选择性捕获循环肿瘤细胞。

Improving performance of cell imprinted PDMS by integrating boronate affinity and local post-imprinting modification for selective capture of circulating tumor cells from cancer patients.

作者信息

Sun Yi, Luo Yi, Sun Lu, Wang Xiao-Rui, Chen Li-Wei, Zhang Ning, Wang Yu, Dong Lin-Yi, Guo Hua, Wang Xian-Hua

机构信息

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.

Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.

出版信息

Biosens Bioelectron. 2023 Mar 1;223:115023. doi: 10.1016/j.bios.2022.115023. Epub 2022 Dec 19.

Abstract

Efficient capture of circulating tumor cells (CTCs) from cancer patients is an important technique that may promote early diagnosis and prognosis monitoring of cancer. However, the existing systems have certain disadvantages, such as poor selectivity, low capture efficiency, consumption of antibodies, and difficulty in release of CTCs for downstream analysis. Herein, we fabricated an innovative PEGylated boronate affinity cell imprinted polydimethylsiloxane (PBACIP) for highly efficient capture of CTCs from cancer patients. The antibody-free PBACIP possessed hierarchical structure of imprinted cavities, which were inlaid with boronic acid modified SiO nanoparticles (SiO@BA), so it could specifically capture target CTCs from biological samples due to the synergistic effect of boronate affinity and cell imprinting. Furthermore, PEGylation was accurately completed in the non-imprinted region by the template cells occupying the imprinted cavity, which not only retained the microstructure of original imprinted cavities, but also endowed PBACIP with hydrophilicity. The artificial PBACIP could efficiently capture human breast-cancer cells from biological sample. When 5 to 500 SKBR3 cells were spiked in 1 mL mice lysed blood, the capture efficiency reached 86.7 ± 11.5% to 96.2 ± 2.3%. Most importantly, the PBACIP was successfully used to capture CTCs from blood of breast cancer patients, and the captured CTCs were released for subsequent gene mutation analysis. The PBACIP can efficiently capture and release CTCs for downstream analysis, which provides a universal strategy toward individualized anti-tumor comprehensive treatments and has great potential in the future cell-based clinical applications.

摘要

从癌症患者体内高效捕获循环肿瘤细胞(CTCs)是一项重要技术,可促进癌症的早期诊断和预后监测。然而,现有系统存在一定缺点,如选择性差、捕获效率低、抗体消耗大以及难以释放CTCs用于下游分析。在此,我们制备了一种创新的聚乙二醇化硼酸亲和细胞印迹聚二甲基硅氧烷(PBACIP),用于从癌症患者体内高效捕获CTCs。无抗体的PBACIP具有印迹腔的分级结构,其中镶嵌有硼酸修饰的SiO纳米颗粒(SiO@BA),因此由于硼酸亲和作用和细胞印迹的协同效应,它可以从生物样品中特异性捕获目标CTCs。此外,通过占据印迹腔的模板细胞在非印迹区域准确完成聚乙二醇化,这不仅保留了原始印迹腔的微观结构,还赋予PBACIP亲水性。人工PBACIP能够从生物样品中高效捕获人乳腺癌细胞。当向1 mL小鼠溶血血液中加入5至500个SKBR3细胞时,捕获效率达到86.7±11.5%至96.2±2.3%。最重要的是,PBACIP成功用于从乳腺癌患者血液中捕获CTCs,并且释放捕获的CTCs用于后续基因突变分析。PBACIP能够高效捕获和释放CTCs用于下游分析,这为个性化抗肿瘤综合治疗提供了一种通用策略,在未来基于细胞的临床应用中具有巨大潜力。

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