Preclinical Systems To Study The Biodistribution Of Nanoparticle Delivery In Pancreatic Ductal Adenocarcinoma

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Pancreatic Ductal Adenocarcinoma (PDA) is a deadly disease, with no effective available treatment. Primary chemoresistance is common and has been attributed to the hypovascularity characteristic of the disease and the dense desmoplastic response that accompanies virtually every case of PDA. Effectively delivering therapeutic anticancer agents to PDA cells is therefore a specific, difficult and understudied problem in PDA that must be resolved for successful treatments to emerge. With the goal of eventually delivering drug payloads via nanoparticles (NP), we used well-defined mouse models of the disease to iteratively test NP distribution to both the cancerous and normal pancreas. Minimal deposition was observed in normal pancreas after intravenous or intraperitoneal administration of a variously sized (25nm or 40nm) NP. Surprisingly, abundant NP deposition was seen in both syngenic xenografted and autochthonous KPC models of PDA. NP deposition tended to be greater with IP administration and was enriched in stoma rich tumor regions. These findings have encouraging ramifications for delivery of depot or novel (e.g. siRNA, radiopharmaceutical, etc.) agents in this deadly disease. 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 2906. doi:1538-7445.AM2012-2906