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A RADIATION ACTIVATED PRODRUG NANOPARTICLE PLATFORM FOR BRAIN CANCER THERAPY by Milan Theodore Makale

A RADIATION ACTIVATED PRODRUG NANOPARTICLE PLATFORM FOR BRAIN CANCER THERAPY

Led by Milan Theodore Makale at University of California, San Diego

This proposal aims to develop a nontoxic, inactive version of a cancer drug, called a prodrug, selectively to brain cancers and not body tissues in general. Low dose radiation directed only at brain tumor areas will trigger prodrug conversion to active drug. This may overcome the notorious resistance of glioblastoma brain cancers by generating high quantities of toxic drug within the tumor. Because the radiation will be low dose and localized, and with prodrug only in the tumor areas, normal tissues will be protected. Also, since radiation can cover large areas, this approach may also destroy the glioblastoma micro-invasions of normal brain tissue that are impossible for the neuro-surgeon to remove. The idea is that the targeted prodrug would accumulate and remain within tumors, while over 12 to 24 hours, it would float away from normal tissue. That way only the main tumor and small invasive tumor sites would have prodrug present during the irradiation. The rest of the body will not be harmed when the prodrug is administered
because the prodrug is nontoxic, and is only converted in brain areas at which the radiation beam is aimed. The prodrug will be made with extremely small structures called nanoparticles. Drug will be linked to the nanoparticle which makes the drug inactive. The nanoparticle lights up when exposed to radiation, freeing the drug and allowing it to be active. Also, many very potent antitumor drugs have a hard time entering the brain so our nanoparticles will be made to cross brain blood vessels throughout the brain. Thus individual cancer cells invading normal brain areas may be engaged by various drugs released from the nanoparticles by carefully directed local irradiation. We envisage this approach as a new standard of patient care to greatly help provide well-tolerated long term control of glioblastoma.

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