Synthesis and in vitro evaluation of a multifunctional and surface-switchable nanoemulsion platform

We present a multifunctional nanoparticle platform that has targeting moieties shielded by a matrix metalloproteinase-2 (MMP2) cleavable PEG coating. Upon incubation with MMP2 this surface-switchable coating is removed and the targeting ligands become available for binding. The concept was evaluated in vitro using the biotin and αvβ3-integrin-specific RGD-peptide functionalized nanoparticles. Intravenously administrable nanoparticles can be used in a variety of biomedical applications that range from targeted drug delivery, target-specific imaging, nucleic acid delivery to thermal therapy.1,2 The nanoparticle coating is of key importance as it greatly influences pharmacokinetics and bioavailability as well as the nanoparticle’s ability to target a diseased site.3 Polymeric coatings, such as a polyethylene glycol (PEG) coating, provide shielding, reduce recognition and subsequent removal by the mononuclear phagocyte system (MPS), and therefore are applied to the majority of nanoparticles used for intravenous administration.1 To enhance specificity and induce nanoparticle uptake by cells, target-specific molecules can be conjugated to the nanoparticle’s coating.1,2 However, th