Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore.
School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, China.
ACS Appl Mater Interfaces. 2020 Mar 25;12(12):13634-13643. doi: 10.1021/acsami.9b21385. Epub 2020 Mar 10.
As an essential DNA repair enzyme, apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in most human cancers and is identified as a cancer diagnostic and predictive biomarker for cancer risk assessment, diagnosis, prognosis, and prediction of treatment efficacy. Despite its importance in cancer, however, it is still a significant challenge nowadays to sense abundance variation and monitor enzymatic activity of this biomarker in living cells. Here, we report our construction of biocompatible functional nanocomposites, which are a combination of meticulously designed unimolecular DNA and fine-sized graphene quantum dots. Upon utilization of these nanocomposites as diagnostic probes, massive accumulation of fluorescence signal in living cells can be triggered by merely a small amount of cellular APE1 through repeated cycles of enzymatic catalysis. Most critically, our delicate structural designs assure that these graphene quantum dot-based nanocomposites are capable of sensing cancer biomarker APE1 in identical type of cells under different cell conditions and can be applied to multiple cancerous cells in a highly sensitive and specific manners. This work not only brings about new methods for cytology-based cancer screening but also lays down a general principle for fabricating diagnostic probes that target other endogenous biomarkers in living cells.
作为一种重要的 DNA 修复酶,脱嘌呤/脱嘧啶核酸内切酶 1(APE1)在大多数人类癌症中过度表达,并被鉴定为癌症风险评估、诊断、预后和治疗效果预测的癌症诊断和预测生物标志物。然而,尽管它在癌症中很重要,但在活细胞中感知这种生物标志物的丰度变化和监测其酶活性仍然是一个重大挑战。在这里,我们报告了我们构建的生物相容性功能纳米复合材料,它是精心设计的单分子 DNA 和精细尺寸的石墨烯量子点的组合。通过将这些纳米复合材料用作诊断探针,通过重复的酶催化循环,仅少量的细胞 APE1 就可以在活细胞中引发大量荧光信号的积累。最重要的是,我们精细的结构设计确保了这些基于石墨烯量子点的纳米复合材料能够在不同细胞条件下相同类型的细胞中感应癌症生物标志物 APE1,并能够以高度敏感和特异的方式应用于多种癌细胞。这项工作不仅为基于细胞学的癌症筛查带来了新方法,而且为在活细胞中针对其他内源性生物标志物制造诊断探针奠定了一般原则。