Targeting Pediatric Brain Tumors Using PTPmu Nanochains with Radiofrequency-Releasable Therapeutics
The invasive forms of pediatric brain tumors, known collectively as high-grade gliomas, are the deadliest form of pediatric cancer. Current therapies offer little hope at extending life. Standard treatment involves maximizing surgical resection, followed by radiation and often chemotherapy. The best outcomes are achieved with maximizing surgical resection. This is nearly impossible, however, because gliomas invade into brain tissue in microscopic, finger-like projections that are invisible to the naked eye and too small to be surgically removed. Chemotherapy is the ideal treatment to target these invasive cells, yet chemotherapy has had limited success in treating pediatric brain tumors. This is likely due to the difficulty of penetrating the blood-brain barrier with standard drugs.
We propose to develop a chain-like nanoparticle that can carry chemotherapeutics with a molecular targeting beacon to target pediatric brain tumors. The chain-like nanoparticle, unlike most drugs and even nanoparticles, can easily cross the blood-brain barrier. The chain-like nanoparticle has been developed to release its drug cargo by mechanical disruption using a radiofrequency signal, thus allowing for maximal drug delivery to the tumor site. To molecularly target the pediatric brain tumors, we will link an agent that binds to a novel PTPmu biomarker present in the tumor microenvironment, which is enriched in pediatric brain tumors, to the chain-like nanoparticle. This system can be used to deliver any drug to pediatric brain tumors. The targeted delivery of therapeutics to pediatric brain tumors will significantly change patient outcomes and reduce off-target treatment related side-effects.