Effects of Docetaxel and Host Immune Status on Nanoparticle Biodistribution and Tumor Uptake

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