肿瘤细胞的准确分类对于癌症诊断和进一步治疗很重要。在这项研究中,我们开发了多分子标记物激活的跨膜DNA计算系统(MTD)。使用细胞膜作为天然门,MTD系统可以在简单的空间事件“跨膜”和“细胞内目标相遇”之后直接输出信号,绕过多步信号转换的需要。MTD系统包括两个智能纳米机器人,能够独立检测三个分子标记(MUC1,EpCAM,和miR-21),进行全面分析。我们的AND-AND逻辑门控系统(MTDAND-AND)表现出特殊的特异性,允许在MCF-7细胞中特异性地靶向释放药物DNA。此外,转换后的OR-AND逻辑门系统(MTDOR-AND)表现出更广泛的适应性,促进三种阳性癌细胞系(MCF-7,HeLa,和HepG2)。重要的是,MTDAND-AND和MTDOR-AND,虽然拥有独特的个性化治疗潜力,共享输出三个成像信号的能力,而无需任何中间转换步骤。此功能可确保跨不同细胞的精确分类(MCF-7,HeLa,HepG2和MCF-10A),即使在混合人群中。这项研究提供了一个简单而有效的解决方案,以增强DNA计算系统的多功能性和准确性。推进其在生物医学诊断和治疗研究中的潜在应用。
Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of \"transmembrane\" and \"in-cell target encounter\", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.