Tuning Surface Functionalities of Sub-10 nm-Sized Nanocarriers to Target Outer Retina in Designing Intravitreal Drug Delivery Agents for Age-Related Macular Degeneration
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Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness, generally affecting people over 50 years of age in industrialized countries. Unfortunately, the anti-vascular endothelial growth factor therapy for AMD rarely showed substantial visual improvements and may result in serious side effects. Combination therapies with a prolonged therapeutic effect and efficient delivery to the intended site are needed, which could be realized through the use of carefully designed nanocarriers. To understand the physicochemical effects of intravitreally administered nanocarriers on their bioavailability, distribution, and targeting efficiency across multiple retinal layers, here we prepared seven different types of surface-functionalized water-soluble dendritic nanocarriers and performed systematic studies. Our findings may provide useful guidelines for the rational design of intravitreal nanocarriers to treat vision-threatening retinal diseases, including AMD.