Radiolabeled Biodistribution of Expansile Nanoparticles: Intraperitoneal Administration Results in Tumor Specific Accumulation

摘要

Nanoparticle biodistribution in vivo is an essential component to the success of nanoparticle-based drug delivery systems. Previous studies with fluorescently labeled expansile nanoparticles, or “eNPs”, demonstrated a high specificity of eNPs to tumors that is achieved through a materials-based targeting strategy. However, fluorescent labeling techniques are primarily qualitative in nature and the gold-standard for quantitative evaluation of biodistribution is through radiolabeling. In this manuscript, we synthesize 14C-labeled eNPs to quantitatively evaluate the biodistribution of these particles in a murine model of intraperitoneal mesothelioma via liquid scintillation counting. The results demonstrate a strong specificity of eNPs for tumors that lasts one to 2 weeks postinjection with an overall delivery efficiency to the tumor tissue of 30 of the injected dose which is congruent with prior reports of preclinical efficacy of the technology. Importantly, the route of administration is essential to the eNP’s material-based targeting strategy with intraperitoneal administration leading to tumoral accumulation while, in contrast, intravenous administration leads to rapid clearance via the reticuloendothelial system and low tumoral accumulation. A comparison against nanoparticle delivery systems published over the past decade shows that the 30 tumoral delivery efficiency of the eNP is significantly higher than the 0.7 median delivery efficiency of other systems with sufficient quantitative data to define this metric. These results lay a foundation for targeting intraperitoneal tumors and encourage efforts to explore alternative, nonintravenous routes, of delivery to accelerate the translation of nanoparticle therapies to the clinic.