Quantum‐Capacitance Biosensing Enables Real‐Time Monitoring of Naxitamab for Therapeutic Response Stratification in Neuroblastoma
Andy Bruno, Ruslán Alvarez‐Diduk, Paula Lara, Gabriel Maroli, Cristina Larrosa, Sandra López‐Miralles, Jaume Mora, Carlos J. Rodríguez‐Hernández, Arben MerkoçiNeuroblastoma, 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.