Quantum-Capacitance Biosensing Enables Real-Time Monitoring of Naxitamab for Therapeutic Response Stratification in Neuroblastoma.
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Neuroblastoma, a leading cause of cancer-related mortality in early childhood, relies on anti-GD2 immunotherapy, whose efficacy is critically dependent on systemic drug exposure that remains largely unmonitored in real time, limiting treatment optimization and early response assessment. Here, a first-in-class, label-free electrochemical biosensing platform is reported for the direct quantification of naxitamab in patient-derived samples. The system is based on a laser-assisted reduced graphene oxide-gold nanoparticle (rGO@AuNPs) nanocomposite, enabling ultrasensitive detection through quantum capacitance modulation arising from perturbations in the electronic density of states of graphene upon biomolecular recognition. Laser-assisted fabrication yields nanostructured electrodes with enhanced surface area and conductivity, promoting stable antibody immobilization and reproducible signal transduction. The platform operates in the femtomolar regime, with a linear response between 25 and 300 fM, high specificity against relevant interferents, and robust performance in diluted human serum. A single-point calibration strategy enables accurate quantification while compensating for device variability. Application to retrospective clinical samples reveals distinct post-infusion concentration profiles, enabling early discrimination between responder groups and detection of antidrug antibody development. This work establishes quantum-capacitance biosensing as a generalizable strategy for real-time monitoring of therapeutic antibodies in precision oncology.