Abstract 5711: Applying new light to the detection and treatment of brain cancers using targeted photodynamic therapy

Abstract

Abstract Currently, an estimated 11.4 million people in the US have been affected by cancer and this number is expected to double by 2020 as indicated by the NIH NCI in 2006. Each year approximately 20% of these people are expected to die of cancer, with brain cancers among the most deadly. Brain cancer patients have a median life expectancy of only 6-10 months after diagnosis, and those with recurring brain cancer survive less than 20 weeks after any therapeutic regime. Consequently, there is a critical need to develop and improve the detection, diagnosis, and treatment of brain cancers, including gliomas. Theranostic drugs have the potential to do all of these and are becoming lifesaving alternatives. However, the current standard of care suffers from lack of specificity and systemic toxicity, often requiring invasive surgical procedures. These are significant obstacles when dealing with minimizing offsite damage to the healthy brain while maximizing treatment efficacy in the tumor. Our study presents a novel drug delivery platform using targeted-gold nanoparticles (Au NP) to deliver a therapeutic photodynamic therapy (PDT) drug, phthalocyanine 4 (Pc 4), across the blood-brain tumor barrier (BBTB), which allows both detection and treatment of gliomas within mere hours. Targeting Pc 4 to cancer-specific biomarkers concentrates the drug specifically at the brain tumor, significantly reducing collateral damage to healthy brain tissue. Once Pc 4 is delivered, it offers selectivity based on its defined light activation. Our targeted delivery vehicle possesses several advantages over systemic drug delivery: greater control over bioavailability of the drug, controlled release of Pc 4 directly to the site, lower concentration of drug required for PDT effect, and avoidance of systemic drug exposure. The drug delivery mechanism of targeted-Au NP Pc 4 was investigated utilizing in vivo and in vitro fluorescence imaging, immunohistochemistry, elemental analysis, biodistribution studies, and therapeutic efficacy. We are able to target cancer biomarkers specifically, deliver hydrophobic drugs across the BBTB, increase drug accumulation into the tumor, alter drug localization, and enhance PDT killing affect. As a result, this study presents a unique application of PDT to the treatment of brain tumors using photosensitizing drugs like Pc 4. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5711. doi:1538-7445.AM2012-5711