Dual-mode photoelectrochemical/colorimetric sensor for CTCs detection based on seaurchin-like LaNiCo/Pd nanozymes and Exo-DNAzyme cascade program

Circulating tumor cells (CTCs) as a new biomarker of liquid biopsy, play an important role in the early diagnosis and dynamic monitoring of cancer, and their precise detection method has attracted increasing attention. Herein, an ultrasensitive and accurate photoelectrochemical (PEC)/visual colorimetric (VCL) dual-mode aptasensing platform is developed for CTCs assay based on lanthanum-doped seaurchin NiCo₂O₄ decorated with palladium (LaNiCo/Pd) nanozymes and Exo-DNAzyme cascade multisignal program. The as-synthesized LaNiCo/Pd nanozymes can not only be used as a multifunctional signal amplifier to significantly weaken the photocurrent of TiO₂ nanospheres, but also efficiently catalyze the 3,3′,5,5′-tetramethylbenzidine (TMB) visual color reaction. The precise identification of aptamer-targeted CTCs not only improves detection specificity, but also activates the cascade amplification of ExoIII and Zn²⁺-DNAzyme. By integrating LaNiCo/Pd nanozymes with Exo-DNAzyme, lower detection limits of 7 and 22 cells/mL for PEC and VCL analysis for A549 cells are achieved. The established aptasensor also effectively distinguishes cancer patients from healthy persons (P < 0.05), indicating the significant potential in early clinical diagnosis. Overall, the developed dual-mode PEC/VCL aptasensing platform as a simple and powerful strategy can meet the on-site point-of-care testing and precise laboratory analysis of CTCs.