Self-enhanced electrochemiluminescence biosensor for acute promyelocytic leukemia detection via resonance energy transfer with GO-ZnO-L-Cys-luminol and Au@Ag nanoparticles.

BACKGROUND: Acute promyelocytic leukemia (APL) is a hematologic malignancy characterized by the PML/RARα fusion gene, which serves as a critical biomarker for early diagnosis, risk stratification, and therapeutic monitoring. However, conventional methods suffer from low sensitivity, complex operation, or high cost, limiting their application in early-stage screening. To address this gap, this study developed an innovative electrochemiluminescence resonance energy transfer (ECL-RET) biosensor with triple-signal amplification for ultrasensitive detection of the PML/RARα fusion gene.

RESULTS: The biosensor core is a rationally designed nanoarchitecture featuring a self-engineered graphene oxide-zinc oxide-l-cysteine-luminol (GO-ZnO-L-Cys-luminol) composite. In this design, GO and ZnO nanoparticles not only enhance electron transfer but also act as a catalytic co-reaction accelerator, while the covalently conjugated L-Cys-luminol serves as a self-enhancing luminophore. This donor system is coupled with a dual-functional Au@AgNPs nanoplatform, which acts as both an efficient energy acceptor and a quencher. Through precise nanoscale spatial regulation, the Au@AgNPs/apDNA-tDNA-cDNA/L-Cys-luminol sandwich assembly achieves optimal donor-acceptor distance for high RET efficiency. Under optimized conditions, the ECL-RET biosensor demonstrated exceptional analytical performance with linear range from 1 × 10-16 to 1 × 10-8 mol/L and a limit of detection (LOD) of 7.4 × 10-17 mol/L.

SIGNIFICANCE: This work provides a robust tool for early APL diagnosis. The proposed triple-amplification strategy and the rational design of the ECL-RET platform offer a generalizable and versatile sensing paradigm, which can be readily adapted for the ultrasensitive detection of a wide range of other disease-related nucleic acid biomarkers and infectious pathogens.