Preparation of nanoparticle-protein complexes for therapeutic application of nanoparticles in ocular diseases

Introduction: Nanoparticles are thought to be novel platforms for therapeutic agents. However, clinical application of nanoparticles lags behind rapid progress in nanotechnology. One of the problems is uncontrolled protein... [ view full abstract ]

Introduction: Nanoparticles are thought to be novel platforms for therapeutic agents. However, clinical application of nanoparticles lags behind rapid progress in nanotechnology. One of the problems is uncontrolled protein adsorption around nanoparticles in the biological fluids, which prohibits intended biological activity. In this study, we investigated the therapeutic potential of nanoparticle-protein complexes which were formed before intraocular injection.

Methods: To investigate corona formation in the ocular environment, we incubated 20- and 100-nm gold and silica nanoparticles in the vitreous fluid of the eye for 24 hours. Then, the corona proteins were identified using proteomic analyses. Biological activities of nanoparticle-protein complexes which were formed with self-assembly of 20-nm gold nanoparticles and the top 5 corona proteins were analyzed with in vitro angiogenesis assays and an in vivo choroidal neovascularization model in mice.

Results: Interestingly, although the compositions of the corona proteins were different from those of the vitreous samples, they each displayed similar patterns independent of the core material or size of nanoparticles. In the vitreous, where protein concentration is less than that of serum or plasma, corona formation is different in its composition patterns. These results highlight the tissue-specific nature of corona formation in the ocular environment. As a novel bio-inspired approach to overcome the loss of intended activity of the nanoparticles due to uncontrolled corona formation, we suggested priming the nanoparticles with tissue-specific corona proteins. Interestingly, the nanoparticle-protein complexes exhibited therapeutic effects by binding with vascular endothelial growth factor that promotes pathological angiogenesis, even in vivo by intraocular injection, better than naïve nanoparticles, which were inevitably exposed to nonspecific protein adsorption.

Discussion: In this study, we investigate tissue-specific formation of corona around locally administered nanomaterials and biological impacts of nanoparticle-protein complexes which were formed before intraocular injection. This strategy, using tissue-specific corona for protection of nanoparticles from non-specific protein adhesion, might extend the applicability of nanoparticle-based therapeutic approaches against various human diseases, especially in local administration.