Synergistic hybrid nanostructures for Ultra-Sensitive photoelectrochemical detection of hepatocellular carcinoma ctDNA

In recent years, the integration of quantum dots (QDs) and upconverting nanoparticles (UCNPs) has emerged as a promising strategy in biomedical research, leveraging QDs' efficient down-conversion and UCNPs' remarkable up-conversion capabilities. This synergy has attracted significant attention for its potential in biomedical applications, particularly in sensitive detection systems. Here, we report the development of a highly sensitive photoelectrochemical (PEC) employing a hybrid nanostructure comprising CdSe QDs and NaYF4:Yb,Er UCNPs. This sensor was specifically tailored for the detection of circulating tumor DNA (ctDNA) with mutations associated with hepatocellular carcinoma (HCC) using synthetic DNA probes. The CdSe QDs and NaYF4:Yb,Er UCNPs were synthesized and integrated using Triton X-100, a non-ionic surfactant. Comprehensive characterization confirmed the successful formation of the hybrid nanostructure, crucial for optimizing sensor performance. Our PEC platform effectively addressed the challenge of detecting single-nucleotide mismatches in HCC ctDNAs, demonstrating superior sensitivity compared to conventional electrochemical methods. Notably, the system exhibited excellent linearity across a broad concentration range (400 aM to 200 pM), surpassing traditional electrochemical approaches. Key to its clinical relevance, the PEC sensor achieved a remarkable limit of detection (2.32 aM) and limit of quantification (15.61 aM), underscoring its potential for early-stage cancer diagnosis as well as very good recovery from spiked samples. This capability is pivotal in overcoming current diagnostic limitations, such as the asymptomatic nature of early-stage HCC and the need for more accurate biomarkers. Our study highlights the promising role of hybrid nanostructures in enhancing biosensor sensitivity and response times, offering a pathway towards improved early detection and management of HCC.