A catalytic hairpin assembly-assisted magnetic SERS platform with core-satellite structure for ultra-sensitive circRNA detection in early lung cancer screening

Lung cancer remains the leading cause of cancer-related deaths worldwide, mainly due to challenges in early detection that often result in poor patient outcomes. In this study, we developed a magnetic biosensing platform based on the coupling of CHA and SERS technologies for one-step detection of lung cancer-related circRNAs. Our approach capitalizes on forming “hot spots” between core–shell SERS nanoprobes and magnetic nanoparticles with precisely defined functionalities, generating a robust Raman signal. This signal is further amplified through magnetic enrichment and calibrated with an internal standard molecule, achieving a remarkably sensitive detection limit of 5.5 aM. Notably, our circRNA detection method significantly surpasses conventional tumor markers’ sensitivity. Validation using human serum samples demonstrated considerably higher circRNA levels in lung cancer patients than healthy controls. Moreover, the core–satellite structured magnetic SERS platform successfully distinguished unique circRNA concentration profiles across early-stage (IA and IB) lung cancers and their subtypes (IA1, IA2, IA3). Collectively, these results underscore the potential of our magnetic SERS platform as a liquid biopsy-based prognostic tool, enhancing early screening sensitivity and thereby facilitating more accurate diagnosis and improved patient stratification.