Organophosphonic Acid‐Functionalized La ^III ‐Bridging Antimonotungstate for Sensitive Electrochemical Biosensing of Circulating Tumor DNA

Cancer recurrence remains a formidable clinical challenge. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for early detection; however, its extremely low abundance in peripheral blood necessitates the development of highly sensitive detection platforms. Herein, an organophosphonic acid (OPA)‐functionalized La III ‐bridging antimonotungstate [H 2 N(CH 3 ) 2 ] 7 Na 12 H 8 {[La 3 W 8 (Hgps) 2 O 20 (H 2 O) 2 ][B‐ α ‐SbW 9 O 33 ] 4 }·66H 2 O ( 1 , H 5 gps = glyphosine) was triumphantly synthesized by a one‐pot assembly strategy with the assistance of CH 3 COOH–CH 3 COONa buffer system. Its polyanion {[La 3 W 8 (Hgps) 2 O 20 (H 2 O) 2 ][B‐ α ‐SbW 9 O 33 ] 4 } 27− is constructed by four trilacunary Keggin [B‐ α ‐SbW 9 O 33 ] 9– building blocks connected via a Hgps 4– ‐functionalized dumbbell‐shaped [La 3 (H 2 O) 2 W 8 (Hgps) 2 O 20 ] 9+ cluster. Alternatively, the polyanion can be viewed as two analogous sandwich‐type [LaW 4 (Hgps) O 10 (B‐ α ‐SbW 9 O 33 ) 2 ] 11– subunits linked through a central La 3+ cation. Taking advantage of the electron‐transfer properties of 1 , its doping into N ‐methylpyrrole (NMPy) via electropolymerization enables the formation of a 1 @PNMPy film with enhanced conductivity and excellent stability. The 1 @PNMPy‐based electrochemical DNA biosensor exhibits remarkable selectivity, anti‐interference capability, stability, and reproducibility. Moreover, it achieves satisfactory recovery rates for ctDNA detection in diluted human serum samples, highlighting its potential for clinical cancer monitoring applications. This work not only provides a novel paradigm for the synthesis of OPA‐functionalized rare earth‐bridged polyoxometalates but also promotes their practical applications in life and health monitoring fields.