Abstract 5401: Investigation of sub-tumor accumulation of PRINT nanoparticles reveals dose and route of administration dependence on particle association

Abstract

Abstract The assessment of nanoparticle accumulation in tumors and other organs uses a whole organ-based approach. These techniques, however, neglect the complex composition of tumors which multiple types of cells other than cancer cells(e.g. endothelial cells, macrophages). For delivery of certain therapeutics, identification of precisely which cells are associating with particles is critical. Using an orthotopic model of melanoma and fluorescently labeled 80x320nm PRINT nanoparticles, we assessed nanoparticle distribution in a cell-type specific manner by flow cytometry. We found that although cancer cells make up 90% of the tumor cells, only a small fraction (1-7%) associate the nanoparticles following intravenous dosing. The fractional association was dependent on the dose used and a plateau is seemingly reached, suggesting a limited number of cells are able to associate with 80x320nm particles. In addition, particle-positive tumor-associated macrophages associated with 4-fold more particles than cancer cells despite constituting approximately 1% of all cells in the tumor. When particles were administered intratumorally, cancer cell association doubles as compared to intravenous dosing. Fluoresence intensity suggests that when dosed intratumorally cancer cells associated with a greater amount of particles, similar to macrophages. Together, these data suggest a biological limitation on the ability of intravenous administration of nanoparticles for nucleic acid delivery and reveal the potential for therapeutic targeting of macrophages. Citation Format: Luke Roode, Tao Bo, Jillian Perry, J. Chris Luft, James E. Bear, Ian J. Davis, Joseph M. DeSimone. Investigation of sub-tumor accumulation of PRINT nanoparticles reveals dose and route of administration dependence on particle association. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5401. doi:10.1158/1538-7445.AM2014-5401