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


Okan M., Çağlayan Arslan Z., Aydın F., ASİL ALPTEKİN D., KÜLAH H.

Microchemical Journal, vol.208, 2025 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 208
  • Publication Date: 2025
  • Doi Number: 10.1016/j.microc.2024.112547
  • Journal Name: Microchemical Journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Food Science & Technology Abstracts, Index Islamicus, Veterinary Science Database
  • Keywords: Biosensor, Circulating tumor DNA, Photoelectrochemistry, Quantum dots, Upconverting nanoparticles
  • Middle East Technical University Affiliated: Yes

Abstract

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.