The structure of iron oxide nanoparticle (IONPs) scaffold influences their pharmacokinetics and biodistribution behavior and provides some guidance on solid tumors uptake, absorption across membrane barriers and targeting organs of the mononuclear phagocyte system (liver, spleen, lungs and lymphoid tissue). We have successfully synthesized superparamagnetic dendronized IONPs and performed in vitro cytotoxicity and in vivo biodistribution studies, as a function of different coatings (Figure 1). 

In vitro MTT and LDH bioviability tests on HepaRG cell line showed no or low toxicity after 48h of incubation for all dendronized NPs, in a large concentration range and up to 80mg/L. Furthermore, in high concentrations, dendronized IONPs promoted cell growth, due to their ability to diminish intracellular H2O2. 

In vivo MRI studies were performed on mice administered with the triple dose used in clinical trials for humans (15µmoles [Fe3+]/kg body weight). Those studies showed a strong negative contrast in the liver in T2-weighted images 90 min after intravenous injection. The negative contrast persisted over 10h in liver and for 6h in bladder. At 24h post injection of dendronized IONPs, the negative contrast for both liver and bladder appeared underneath 20%, suggesting their susceptibility to renal and hepato-biliary excretion. Furthermore, despite the administered dose, all mice showed no toxic signs over 48h, e.g. mice showed regular breathing, good quality walkways, no surrounding tissue irritation.

Results obtained in the present work provide a strong basis for future cooperation with Dr. Sophie Laurent on in vivo MRI studies, in developing nano-conjugates with higher contrast enhancement effect and with active targeting for apoptosis.