The SERS sensing of nucleic acids (DNA) by coating the plasmonic materials with a biocompatible layer and complementary DNA strands developed an entire stimulating area in biomedical applications, specifically for the diagnosis of malignant diseases. However, the labels and coating increase the overall hydrodynamic size of the plasmonic nano-materials, which restricts the internalization inside the nucleus, and DNA sensing stays limited to the sensing of cytoplasmic DNA or isolated DNA strands. To elucidate this, here we introduce the concept of sensing the intracellular DNA in the in vitro environment by using small plasmonic sensors for cancer diagnosis. As far as we know, it is the first attempt to study the native plasmonic sensors for the sensing of intracellular DNA molecules without the need for surface labels and coatings. Here, the plasmonic sensors were able to successfully self-internalize inside the cellular nucleus by diffusion mechanism because of its extremely small size (2.3 nm). Due to the presence of plasmonic sensors inside the nucleus, the DNA signal’s intensity significantly increases by a minimum of 700 folds. The SERS signals resulted in the simultaneous sensing of multiple cellular components, which can be used for the analysis of cancer. Therefore, by using Principal Component Analysis (PCA) and Hierarchical Clustering analysis, we can analyze a significant difference between malignant (lung cancer and pancreatic cancer) and healthy cells. In addition to differentiating between cancerous and healthy cells, we were able to differentiate lung cancer cells from pancreatic cancer cells. The native plasmonic sensors were synthesized by using physical synthesis methods (laser synthesis), which eliminates the need for labels and surface coating, as the sensors are synthesized without residues. This indicates that the physically synthesized sensors can sense the DNA molecules in the in vitro environment without losing signals or distortion. The present study holds a promising potential for developing a new technique for accurate diagnosis of the cancer-based on cell DNA diagnosis.

通过用生物相容性层和互补DNA链包裹等离激元材料，对核酸（DNA）进行SERS感测在生物医学应用中发展了整个刺激区域，特别是用于恶性疾病的诊断。然而，标记物和涂层增加了等离子体纳米材料的整体流体动力学尺寸，这限制了核内的内在化，并且DNA感测仍然局限于对细胞质DNA或分离的DNA链的感测。为了阐明这一点，在这里我们介绍在体外感应细胞内DNA的概念通过使用小型等离子体传感器进行癌症诊断。据我们所知，这是首次研究无需表面标记和涂层即可检测细胞内DNA分子的天然等离子体传感器。在这里，等离子传感器由于其极小的尺寸（2.3 nm）而能够通过扩散机制成功地自我内在化。由于核内存在等离激元传感器，DNA信号的强度显着增加了至少700倍。SERS信号导致同时感测多个细胞成分，可用于癌症分析。因此，通过使用主成分分析（PCA）和分层聚类分析，我们可以分析恶性肿瘤（肺癌和胰腺癌）与健康细胞之间的显着差异。除了区分癌细胞和健康细胞外，我们还能够区分肺癌细胞和胰腺癌细胞。通过使用物理合成方法（激光合成）来合成天然等离激元传感器，因为无需残渣即可合成传感器，因此无需标记和表面涂层。这表明物理合成的传感器可以感应到 由于传感器合成时没有残留物，因此无需标签和表面涂层。这表明物理合成的传感器可以感应到 由于传感器合成时没有残留物，因此无需标签和表面涂层。这表明物理合成的传感器可以感应到在体外环境中不会丢失信号或失真。本研究具有开发基于细胞DNA诊断的准确诊断癌症新技术的潜在潜力。