High Affinity Fluorescent Nanoparticles For Detection Il13r.2-Positive Extracellular Vesicles And Cells

Abstract Glioblastoma (GBM) is both the most common and deadly malignant primary brain tumor with a 1-year survival of 37.2% and a 5-year survival of just 5.1%. The standard of care for GBM is surgical excision followed by radiation with concurrent and adjuvant temozolomide-centered chemotherapy (TMZ). Despite advances in imaging technology, early identification of treatment failure or impending resistance remains problematic. A unique characteristic of GBM is the overexpression of the α2 variant of IL-13 receptor (IL13Rα2) in 78–96% of patients while virtually undetectable in normal brain tissue. We hypothesize that the blood of patients with GBM contains sufficient IL13Rα2-positive extracellular vesicles (EV) to inform the clinical picture regarding disease status such as tumor recurrence and response to therapy. To detect IL13Rα2 as a specific molecular target for diagnostic testing, we have developed a modified version of IL-13 with increased affinity and specificity for IL13Rα2, and conjugated this ligand to fluorescent/ magnetic nanoparticles using an 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) linker. Furthermore, we demonstrated that the EV plasma fraction of patients with GBM is enriched for the IL13Rα2 receptor. We also demonstrated the ability of the ligand-bound nanoparticles to aggregate with IL13Rα2-positive cells and EVs in vitro. This ligand-based affinity purification particle has the potential to both quantify IL13Rα2 EV levels in patient blood and isolate these EVs for further interrogation of genomic and proteomic molecular markers.