Abstract 4449: Deep penetration of PDT drugs into tumors via non-covalent drug-gold nanoparticle conjugates

Abstract

Abstract In 2010, more than a million new cancer cases are expected to be diagnosed with half resulting in death, at an NIH estimated total yearly cost of $263.8 billion. Therefore, there is a critical need to improve both cancer diagnostics and therapeutics; future theranostics aim to combine both in a single visit. Consequently, efficient delivery of hydrophobic, theranostic drugs is necessary. This study presents a novel non-covalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system that is able to perform rapid drug release deep into tumors within hours rather than days. The drug delivery mechanism of the PDT drug Pc 4 using Au NPs into tumors by passive accumulation was investigated via fluorescence imaging of Pc 4, elemental gold analysis, and histological staining. The pharmacokinetics of the conjugates over a 7 day period showed rapid drug excretion, as monitored via the fluorescence of Pc 4 which decreased significantly to near baseline levels. Moreover, the biodistribution of Au NPs indicated clearance of the conjugates from the mice. The spleen, liver, kidneys, and urinary tract showed accumulation of Au NPs and accounted for 33.6% of the injected dose at only 4 hrs, suggesting possible excretion pathways, since the total injected dose of Au NPs recovered from dissected organs decreased by 33.4%. Histological analysis corroborated these findings; Au NPs in the liver were found in liver sinusoids and hepatocytes, Au NPs in the spleen were found near macrophages, Au NPs in the kidney were located in the glomerulus, and Au NPs in the urinary tract were found in the stroma. At 4 hrs post-injection, ∼76% of the injected dose of Au NPs was recovered in harvested organs, and AuNPs accumulated passively in tumors with an average accumulation of 8 ± 6 % ID (or ∼62.46 μg/g of tumor tissue). The tumor (4 hrs post-injection) showed very high fluorescence intensities further suggesting the passive accumulation of Pc 4 via the Au NPs within the tumor. In vitro studies showed the conjugates delivered 389.4 moles of Pc 4 per mole of Au NP into cells in 4 hrs; in vivo studies showed approximately 10 RFUs (of Pc 4)/ μg of gold delivered into tumor tissues. Ultimately, this study suggests that Pc 4 non-covalently loaded Au NPs that penetrate deep into the tumor interior provide a very attractive approach to delivery cancer drugs to visualize carcinomas and track therapeutic responses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4449. doi:10.1158/1538-7445.AM2011-4449