Furry nanoparticles: synthesis and characterization of nanoemulsion-mediated core crosslinked nanoparticles and their robust stability in vivo

Reinforcement of the in vivo structural stability of polymer-based nanoparticles such as polymeric micelles has been achieved via covalently crosslinked structures. Herein, we report new core crosslinked nanoparticles prepared via an o/w nanoemulsion composed of difunctional polymerizable oil monomers stabilized by a poly(ethylene glycol) (PEG)-bearing surfactant. The obtained PEG-tethered core crosslinked nanoparticles are named furry nanoparticles (f-NPs). The f-NPs’ structure was evaluated using light scattering (LS; both static SLS and dynamic DLS), small-angle X-ray scattering, and transmission electron microscopy. The f-NPs’ size could be easily controlled by changing the amount of oil monomer, which also affected dye loading and releasing behavior. Employing a disulfide-based oil monomer, we could endow the f-NPs with sensitivity to reduction, demonstrating destabilization in a reducing environment with a high glutathione level matching that in tumors. The structural stability of f-NPs in vivo was very high compared with that of a micellar system, resulting in prolonged circulation in the bloodstream. Interestingly, the in vivo stability might depend on the crowding density of PEG chains at the outermost surface, even though the structural stability was guaranteed by the crosslinked structure. This study demonstrates the promising synthesis of core crosslinked nanoparticles and their potential as drug carriers.