Synergistic drug combination screening using a nanodroplet processing platform to enhance neuroblastoma treatment in TH-MYCN transgenic mice.

Neuroblastoma is a highly aggressive pediatric cancer with a poor prognosis, particularly in high-risk (HR) cases characterized by MYCN amplification. The severe side effects associated with high-dose chemotherapy further complicate treatment. Despite significant advancements in drug screening, traditional platforms remain limited due to their requirement for large cell quantities and their low translational success from bench to clinic. These limitations hinder the application of personalized medicine screening for patients with neuroblastoma. To address these challenges, we developed a Bioinspired Nanodroplet Processing (BioNDP) platform. This innovative platform allows for the simultaneous screening of multiple drug combinations while reducing the required number of cells to just 100 and minimizing assay volumes to 200 nL per well. Using BioNDP, we screened chemotherapeutic combinations of cyclophosphamide, doxorubicin, and vincristine in both the SK-N-DZ neuroblastoma cell line and primary neuroblastoma cells derived from TH-MYCN transgenic mice. Our findings revealed a specific drug combination that exhibited significant synergistic cytotoxicity in neuroblastoma cells. This combination completely eradicated tumors and significantly improved survival rates in TH-MYCN mice, without notable side effects. This study highlights the potential of the BioNDP platform in bridging in vitro and in vivo results, offering a promising strategy for personalized medicine in the treatment of HR neuroblastoma, with reduced toxicity and enhanced therapeutic efficacy.