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Abstract
Selective delivery of gold nanorods (GNRs) to sites of prostate tumor angiogenesis is potentially advantageous for localized photothermal therapy. Here, we report the cellular uptake and biodistribution of GNRs surface functionalized with the cyclic RGDfK peptide. The GNRs were synthesized to have a surface plasmon resonance (SPR) peak at 800 nm and grafted with a thiolated poly(ethylene glycol) (PEG) corona with or without RGDfK. The binding and uptake of the targeted (RGDfK) and untargeted GNRs were evaluated in DU145 prostate cancer and human umbilical vein endothelial cells (HUVEC) by high-resolution dark field microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). The biodistribution of both GNRs was then evaluated in prostate tumor bearing mice. Targeting of the RGDfK surface-modified GNRs was confirmed in vitro due to selective binding and uptake by endothelial cells. Tumor targeting was not observed in vivo, however, due to fast clearance of the RGDfK-GNRs from the blood. Further modifications of the nanoparticle’s surface properties are needed to enhance localization of the targetable system in sites of tumor angiogenesis.
Acknowledgment
The authors thank Diego Fernandez for his ICP-MS support as well as Nancy Chandler for her help with the TEM images taken. The authors would also like to acknowledge Josh Gustafson, Robert Price, and Khaled Greish for their help with the animal studies.
Declaration of interest
The authors have a patent pending application relevant to this work. This research was supported by a Department of Defense Prostate Cancer Predoctoral Training Award (PC094496) as well as the National Institutes of Health (R01-DE19050 and EB-R01EB7171) and the Utah Science Technology and Research (USTAR) Initiative.