Department of Biomedical Engineering, School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China.
Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Nanoscale. 2023 Aug 25;15(33):13834-13841. doi: 10.1039/d3nr02665e.
Selecting 1st-line treatment for lung cancer is currently a binary choice, either chemotherapy or targeted medicine, depending on whether EGFR mutations exist. Next-generation sequencing is fully capable of accurately identifying EGFR mutations and guiding the usage of tyrosine kinase inhibitors, but it is highly expensive. Moreover, as the sequencing is not helpful for patients with wild-type EGFR, the long wait for sequencing may delay the chemotherapy and correspondingly increase the risks of cancer progression. To address this issue, a new method for rapidly determining the presence of EGFR mutations is developed in this study. A series of DNA origami-engineered nanocalipers are designed and constructed to determine the EGFR spatial distribution of either mutated EGFR or wild-type EGFR lung cancer cells. The experimental results on cancer cell lines and 9 clinical tissue samples show that compared with wild-type EGFR cells, mutated EGFR cells have narrower EGFR spacing. Hence, the DNA nanocalipers are demonstrated to be capable of determining the presence of EGFR mutations and shrinking the detection period from weeks to hours, compared with sequencing. For determining EGFR mutation status in 9 clinical samples, DNA nanocalipers show 100% consistency with next-generation sequencing.
选择肺癌一线治疗方案目前是一个二元选择，要么化疗，要么靶向药物，取决于是否存在 EGFR 突变。下一代测序完全能够准确识别 EGFR 突变并指导酪氨酸激酶抑制剂的使用，但费用非常高。此外，由于测序对 EGFR 野生型患者没有帮助，因此长时间等待测序可能会延迟化疗，并相应增加癌症进展的风险。针对这一问题，本研究开发了一种快速确定 EGFR 突变存在的新方法。设计并构建了一系列 DNA 折纸工程纳米卡尺，以确定突变型 EGFR 或野生型 EGFR 肺癌细胞中 EGFR 的空间分布。在癌细胞系和 9 个临床组织样本上的实验结果表明，与野生型 EGFR 细胞相比，突变型 EGFR 细胞的 EGFR 间距更窄。因此，与测序相比，DNA 纳米卡尺能够确定 EGFR 突变的存在，并将检测周期从几周缩短到几小时。对于 9 个临床样本中 EGFR 突变状态的确定，DNA 纳米卡尺与下一代测序具有 100%的一致性。
