<i>In vivo</i> selection of anti-glioblastoma DNA aptamers in an orthotopic patient-derived xenograft model

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor of adults. Current therapeutic options yield dismal prognoses that have remained essentially unchanged over nearly two decades. Diffuse growth patterns, high intratumoral heterogeneity, and variable blood-brain barrier integrity limit treatment efficacy, creating challenges that rational small molecule design has not overcome. Antibody-drug conjugates have shown some promise, leading us to hypothesize that smaller folded DNA aptamers, developed <i>in vivo</i> via principles of natural selection, might eventually have advantages for drug delivery. Here, we document the first <i>in vivo</i> DNA aptamer selection involving an orthotopic patient-derived xenograft GBM mouse model to identify tumor-homing DNA aptamers. We demonstrate the preferential accumulation of these aptamers in the tumor relative to other tissues 4 h after intraperitoneal injection. The aptamers can be detected by quantitative polymerase chain reaction, fluorescent tumor staining, and stain GBM tumor section from untreated mice and the GBM tumor cells in culture. Two of three candidates are selective for the target cell line <i>in vitro</i> and do not bind other human tumor cells. <i>In vivo</i> selection of tumor-specific DNA aptamers demonstrates a novel approach for diagnostics or toxin delivery that might allow for the development of individualized therapies.