Renal clearing iron oxide nanoparticles for tumor integrin targeting

Objectives Iron oxide nanoparticles (IONPs) with superior magnetic properties and targeting specificity hold great promise as the next generation contrast agent in magnetic resonance imaging (MRI). However, most of the particles have relatively large hydrodynamic particle sizes and consequently short circulation half-life and rapid reticuloendothelial system (RES) uptake. The goal of this study is to develop a renal clearing IONP conjugate for tumor specific targeting.

Methods An amphiphilic triblock co-polymer was applied to coat onto iron oxide nanoparticles, making which water soluble and function-extendable. These particles were then labeled with an organic dye IRDye800, and were covalently coupled with cyclic RGD peptides for rendering tumor targeting capability. The optical/MR probe was then tested both in vitro and in vivo.

Results The r₂ value for the newly developed IONPs was estimated to be 190 mmol^-1s^-1. The RGD conjugated IONPs showed integrin specific uptake in integrin positive U87MG tumor cells. In vivo studies performed on U87MG glioblastoma xenograft model showed that, the particles, after intravenous injection, could specifically home to tumor areas, which was tracked through by both MRI and NIR fluorescence imaging. More interestingly, a significant renal clearance and inhibited liver uptake was observed.

Conclusions Overall, we demonstrated that it is possible to integrate specific targeting and renal clearance, two seemingly contradictory concepts, into one modality.