T₁-Enhanced MRI-visible nanoclusters for imaging-guided drug delivery

Iron oxide nanoparticles with extremely low dimensions have recently been explored as positive (T₁) contrast agent for magnetic resonance imaging (MRI). However, their small sizes lead to fast renal clearance and limit their use in elongated in vivo tracking or therapy monitoring. In this paper, we present a state of art approach to forming nanoclusters by crosslinking ultrasmall iron oxide nanoparticles with bovine serum albumin. This novel design not only maintains the T₁ performance of the ultrasmall nanoparticles, but also significantly increases their blood circulation times from 15 minutes to over two hours. Our breast tumor model study also exhibited enhanced contrast at tumor sites for more than 24 hours. The ability of maintaining the T₁ performance of the ultrasmall nanoparticles is significant, because previous studies have shown complete T₁ loss or signal decrease upon polymer encapsulation. This design also shows great potential in encapsulating model drug molecules, which will greatly benefit the field of imaging-guided drug delivery.