Microbubbles decorated with dendronized magnetic nanoparticles for biomedical imaging: effective stabilization via fluorous interactions

Dendrons fitted with three oligo(ethylene glycol) (OEG) chains, one of which contains a fluorinated or hydrogenated end group and bears a bisphosphonate polar head (C(n)X(2)(n)(+1)OEG(8)Den, X = F or H; n = 2 or 4), were synthesized and grafted on the surface of iron oxide nanoparticles (IONPs) for microbubble-mediated imaging and therapeutic purposes. The size and stability of the dendronized IONPs (IONP@C(n)X(2)(n)(+1)OEG(8)Den) in aqueous dispersions were monitored by dynamic light scattering. The investigation of the spontaneous adsorption of IONP@C(n)X(2)(n)(+1)OEG(8)Den at the interface between air or air saturated with perfluorohexane and an aqueous phase establishes that exposure to the fluorocarbon gas markedly increases the rate of adsorption of the dendronized IONPs to the gas/water interface and decreases the equilibrium interfacial tension. This suggests that fluorous interactions are at play between the supernatant fluorocarbon gas and the fluorinated end groups of the dendrons. Furthermore, small perfluorohexane-stabilized microbubbles (MBs) with a dipalmitoylphosphatidylcholine (DPPC) shell that incorporates IONP@C(n)X(2)(n)(+1)OEG(8)Den (DPPC/Fe molar ratio 28:1) were prepared and subsequently characterized using both optical microscopy and an acoustical method of size determination. The dendrons fitted with fluorinated end groups lead to smaller and more stable MBs than those fitted with hydrogenated groups. The most effective result is already obtained with C(2)F(5), for which MBs of ≈1.0 μm in radius reach a half-life of ≈6.0 h. An atomic force microscopy investigation of spin-coated mixed films of DPPC/IONP@C(2)X(5)OEG(8)Den combinations (molar ratio 28:1) shows that the IONPs grafted with the fluorinated dendrons are located within the phospholipid film, while those grafted with the hydrocarbon dendrons are located at the surface of the phospholipid film.