HG-119: TARGETED DELIVERY OF TEMOZOLOMIDE TO BRAIN TUMORS USING MICELLE-BASED THERANOSTICS

Current standard of care TMZ, a DNA alkylating pro-drug, is very toxic when delivered systemically; therapeutic dosages are limited by severe side effects. These factors necessitate a selectively targeted carrier for TMZ to deliver the drug efficiently, avoid nonspecific interaction, and reduce offsite toxicity. We address these issues using a tailored surface to attach biomolecules for targeting, a biocompatible coating to encapsulate the drug, and stimuli-induced disruption of the carrier for controlled drug release. Micelles containing drug are synthesized and a short PDGF peptide is conjugated to the micelle. These micelles have also been labeled with a NIR fluorophore for tracking. These micelles have the advantage of small size to cross blood-brain barrier and reduced toxicity due to robust packaging of TMZ drug inside the core. Cellular uptake studies demonstrate significant uptake of the PDGFR-targeted micelles. In vivo studies demonstrate selective accumulation of TMZ in orthotopic gliomas implanted in mice.