Biocompatible engineered erythrocytes as plasmonic sensor initiators for high-sensitive screening of non-small cell lung cancer-derived exosomal miRNA in an integrated system

The development of a holistic solution is crucial for exosome-based liquid biopsy, which is a significant advancement from basic research to clinical application for the early and non-invasive diagnosis of disease. However, the challenge of current technology is how to facilitate the separation and quickly connect with the detection. Herein, employing miRNA-155 as a target, a novel integrated concentration and determination system of exosomes (ICDSE) was fabricated for the targeted enrichment of exosomes from the plasma of patients with non-small cell lung cancer and instant downstream analysis of exosomal miRNA. This ICDSE consists of aptamer-engineered erythrocytes with a supramolecular plasmonic biosensor. The streamlined analytical procedure benefited from engineered erythrocytes as an interlinkage, needlessly removing them before extracting total RNA due to the lack of nuclei. With the assistance of a specific aptamer and simple centrifugation, engineered erythrocytes achieved exceptional enrichment of exosomes within 30 min. The LOD of the biosensor for miR-155 approached 2.03 fM due to the substantially high refractive index of the quadruplet supramolecular dendrimer and zirconium metal-organic framework. Impressively, the developed ICDSE successfully isolated and evaluated exosomes from clinical specimens of patients with NSCLC, which can also be promising for other diseases with identifiable exosome signatures. Thus, our ICDSE is expected to have widespread biomedical applications, as it is economical and well-accepted.