Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
Renmin Hospital of Wuhan University , Wuhan 430060, China.
ACS Nano. 2016 Jun 28;10(6):6201-10. doi: 10.1021/acsnano.6b02208. Epub 2016 Jun 17.
Isolation of single circulating tumor cells (CTCs) from patients is a very challenging technique that may promote the process of individualized antitumor therapies. However, there exist few systems capable of highly efficient capture and release of single CTCs with high viability for downstream analysis and culture. Herein, we designed a near-infrared (NIR) light-responsive substrate for highly efficient immunocapture and biocompatible site-release of CTCs by a combination of the photothermal effect of gold nanorods (GNRs) and a thermoresponsive hydrogel. The substrate was fabricated by imprinting target cancer cells on a GNR-pre-embedded gelatin hydrogel. Micro/nanostructures generated by cell imprinting produce artificial receptors for cancer cells to improve capture efficiency. Temperature-responsive gelatin dissolves rapidly at 37 °C; this allows bulk recovery of captured CTCs at physiological temperature or site-specific release of single CTCs by NIR-mediated photothermal activation of embedded GNRs. Furthermore, the system has been applied to capture, individually release, and genetically analyze CTCs from the whole blood of cancer patients. The multifunctional NIR-responsive platform demonstrates excellent performance in capture and site-release of CTCs with high viability, which provides a robust and versatile means toward individualized antitumor therapies and also shows promising potential for dynamically manipulating cell-substrate interactions in vitro.
从患者中分离单个循环肿瘤细胞 (CTC) 是一项极具挑战性的技术,它可能会促进个体化抗肿瘤治疗的进程。然而,目前能够高效捕获和释放具有高活力的单个 CTC 以用于下游分析和培养的系统很少。在此,我们设计了一种近红外 (NIR) 光响应基底,通过金纳米棒 (GNR) 的光热效应和温敏水凝胶的组合,实现了 CTC 的高效免疫捕获和生物相容的位点释放。该基底通过在预先嵌入 GNR 的明胶水凝胶上压印靶癌细胞来制备。细胞压印产生的微/纳米结构为癌细胞产生了人工受体,从而提高了捕获效率。温度响应明胶在 37°C 时迅速溶解;这允许在生理温度下批量回收捕获的 CTC,或通过嵌入 GNR 的 NIR 介导的光热激活来特异性释放单个 CTC。此外,该系统已应用于从癌症患者的全血中捕获、逐个释放和遗传分析 CTC。多功能 NIR 响应平台在高活力的 CTC 捕获和位点释放方面表现出优异的性能,为个体化抗肿瘤治疗提供了一种强大而通用的手段,并且在体外动态操纵细胞-基底相互作用方面也显示出了有前途的潜力。