Multifunctional Nanotherapeutics with Long-Acting Release against Macular Degeneration by Minimally Invasive Administration

Neovascular age-related macular degeneration (AMD), a leading cause of blindness, requires frequent intravitreal injection of antivascular endothelial growth factor (anti-VEGF), which could generate a succession of complications with poor patient compliance. The current VEGF-targeting therapies often fail in half of patients due to the complex pathologic microenvironment of excessive reactive oxygen species (ROS) production, and increased levels of inflammation are accompanied by choroidal neovascularization (CNV). We herein reported multifunctional nanotherapeutics featuring superior antioxidant and anti-inflammation properties that aim to reverse the pathological condition, alongside its strong targeted antiangiogenesis to CNV and its ability to provide long-term sustained bioactive delivery via the minimally invasive subconjunctival injection, so as to achieve satisfactory wet AMD treatment effects. Concretely, the nanomedicine was designed by coencapsulation of astaxanthin (AST), a red pigmented carotenoid known for its antioxidative, anti-inflammatory and antiapoptotic properties, and axitinib (AXI), a small molecule tyrosine kinase inhibitor that selectively targets the vascular epidermal growth factor receptor for antiangiogenesis, into the Food and Drug Administration (FDA) approved poly(lactic-