Poly(ethylene glycol)-alendronate coated nanoparticles for magnetic resonance imaging of lymph nodes

Nanoparticulate systems can passively target regional lymphatic vessels and lymph nodes (LNs) after interstitial administration. Highly sensitive non-invasive imaging techniques, such as magnetic resonance imaging (MRI), can take advantage from particles' lymphotropic properties to provide a reliable tool to monitor lymphatic function and LN morphology with high spatial resolution. In this work, we developed and characterised a bioerodible nanosystem with MRI contrast properties, based on poly(ethylene glycol)-alendronate stabilised gadolinium calcium phosphate nanoparticles (NPs). After foot paw injection in mice, the particles exhibited a distinct pattern of gradual uptake into the local lymphatics and a localised deposition in the popliteal LN. Less variability in the onset of the signal, intensity and localisation was observed compared to the commercially available tracer gadobutrol, suggesting that these NPs could be useful to monitor physiological and dysfunctional lymphatic conditions. Moreover, dissolution of the particles indicated that they would be rapidly cleared from the body after imaging. Nevertheless, our findings call for an improvement of the system that includes reduction of gadolinium leakage from the NPs, and decrease in size of the latter to increase their selective uptake by the LN.