and was raised there and in Ottawa, Ontario. He received a B.A.Sc. in 2004 in systems design engineering from the University of Waterloo. He obtained a M.Sc. in biochemistry in 2007 from McMaster University under the supervision of Dr. David Andrews. He is presently completing a Ph.D. at the Institute for Biomaterials and Biomedical Engineering at the University of Toronto with Dr. Gang Zheng. His research interests are in the fascinating world of nanoscale bioengineering, including activatable fluorophores and photosensitizers for imaging and therapy. Tracy W. B. Liu graduated with a B.Sc. from the University of British Columbia in 2007. She is currently pursuing a Ph.D. at the University of Toronto in the department of Medical Biophysics under the cosupervision of Dr. Brian Wilson and Dr. Gang Zheng. Her doctorate studies are focused on the development of molecular beacons and their application in cancer diagnosis and therapeutics.

Understanding the principles governing the design of nanoparticles for tumor targeting is essential for the effective diagnosis and treatment of solid tumors. There is currently a poor understanding of how to rationally engineer nanoparticles for tumor targeting. Here, we engineered different-sized spherical gold nanoparticles to discern the effect of particle diameter on passive (poly(ethylene glycol)-coated) and active (transferrin-coated) targeting of MDA-MB-435 orthotopic tumor xenografts. Tumor accumulation of actively targeted nanoparticles was found to be 5 times faster and approximately 2-fold higher relative to their passive counterparts within the 60 nm diameter range. For 15, 30, and 100 nm, we observed no significant differences. We hypothesize that such enhancements are the result of an increased capacity to penetrate into tumors and preferentially associate with cancer cells. We also use computational modeling to explore the mechanistic parameters that can impact tumor accumulation efficacy. We demonstrate that tumor accumulation can be mediated by high nanoparticle avidity and are weakly dependent on their plasma clearance rate. Such findings suggest that empirical models can be used to rapidly screen novel nanomaterials for relative differences in tumor targeting without the need for animal work. Although our findings are specific to MDA-MB-435 tumor xenografts, our experimental and computational findings help to enrich knowledge of design considerations that will aid in the optimal engineering of spherical gold nanoparticles for cancer applications in the future.

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