ID #467 MiR-19-based detection of SHH subtype medulloblastoma recurrence via new single-walled carbon nanotube (SWCNT) optical nanosensor

Abstract

Medulloblastoma (MB) is the most common solid malignant brain tumor in children, with a five-year survival of ∼70-80%. Nevertheless, nearly ∼30% of patients experience recurrence, resulting in only 18% survival rate at three years. Although MRI can identify asymptomatic relapse, its clinical value is limited by low sensitivity, technical challenges, and associated sedation risks. MicroRNAs (miRNAs), small non-coding RNAs, remain stable in biofluids and may reflect tumor status and therapeutic response, making them strong biomarker candidates. We aim to detect early MB recurrence using a nanotechnology platform that rapidly and sensitively identifies biomarkers in vivo and from liquid biopsies ex vivo. Using a Sonic Hedgehog (SHH)-MB mouse model (Ptf1acre/+;Ptch1fl/fl), we profiled exosomal miRNAs from primary MB tissue explants and plasma. Members of the miR-17∼92 cluster and its paralogs were among the most highly secreted miRNAs in advanced SHH-MB explants, comprising the top 6% of ∼400 profiled miRNAs. Exosomal miR-17∼92 components were also present in MB patient plasma but not in healthy controls. MiR-19, a key cluster member, was detected in plasma from late-stage SHH-MB mice and was the only miRNA significantly associated with progression from early hyperplasia to advanced MB, with levels declining after radiation treatment. Our prior work has shown that single-walled carbon nanotube (SWCNT) nanosensors can detect local miR-19 across multiple biofluids, supporting its use as a recurrence biomarker. We are developing a hydrogel-encapsulated SWCNT optical nanosensor for non-invasive, longitudinal detection of miR-19 (or other miRNAs) hybridization events. This nanosensor can be implanted into the resection cavity of SHH-MB mice to enable non-invasive monitoring of local tumor recurrence through in vivo miR-19 detection. Members of the miR-17∼92 cluster, particularly miR-19, emerge as promising biomarkers for primary MB progression and potential recurrence. SWCNT nanosensors could provide a non-invasive approach for early MB detection.