Effects of Docetaxel\nand Host Immune Status on Nanoparticle\nBiodistribution and Tumor Uptake

Despite promising preclinical research on nanoparticle-based\nstrategies\nfor improving cancer therapeutics, their clinical translation remains\nlimited. The efficacy of these strategies often depends on the efficient\ndelivery of nanoparticles to the tumor environment, making accurate\nrepresentations of their biodistribution paramount in evaluating their\npotential. However, many studies commonly employ immunodeficient animal\nmodels to assess their therapeutic efficacy. While useful, these models\ndo not accurately depict nanoparticle interactions with the immune\nsystem, which could lead to results being overstated due to the misrepresentation\nof their biodistribution. In our study, we demonstrate that immunocompetent\nmouse models exhibit significant alterations to the biodistribution\nof gold nanoparticles compared to conventional immunodeficient mouse\nmodels. The presence of a fully functional murine immune system was\nfound to significantly increase the accumulation of gold nanoparticles\nin phagocytosing organs, consequently decreasing the concentration\nin tumors up to 95%, highlighting the importance of employing syngeneic\ntumor models to better predict clinical performance. Furthermore,\nwe show that the concurrent administration of the chemotherapeutic\nagent docetaxel can assist in remediating this decrease by significantly\nenhancing gold nanoparticle accumulation in syngeneic tumors, demonstrating\nits potential as a combinatorial approach with nanoparticle-based\ncancer therapeutics. Based on our results, this elicits further investigation\non the interactions of immune cells with gold nanoparticles and surface\nligands used in our study to fully optimize their delivery to tumors.