Cellular DNA based cancer diagnosis using self-internalized plasmonic sensors

Abstract

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.