Targeting the choroidal neovascularization microenvironment: new perspectives in nanotherapeutic strategies

Choroidal neovascularization (CNV) is a key pathological mechanism underlying irreversible vision loss in diseases such as age-related macular degeneration (AMD). Although anti-vascular endothelial growth factor (VEGF) therapies effectively inhibit angiogenesis, they are limited by the need for frequent injections, the tendency to induce resistance, and their inability to reverse the complex pathological microenvironment driving CNV. Research indicates that the initiation and progression of CNV are cooperatively driven by the local microenvironment, particularly through the interplay of oxidative stress, hypoxia, and inflammatory networks. In recent years, the emergence of nanotechnology has provided unprecedented tools for precise modulation of this microenvironment. This review systematically delineates the mechanisms of CNV formation, with a focused analysis on the core interplay between oxidative stress, hypoxia, and inflammation. We provide an in-depth exploration of advanced nano-therapeutic strategies designed to multi-target angiogenic pathways, dynamically manipulate reactive oxygen species, disrupt hypoxia-driven feedback loops, reprogram the immunoinflammatory network, and restore defective cellular autophagy. This review aims to provide a theoretical foundation and forward-looking perspective for developing next-generation microenvironment-targeted therapies capable of intervening in CNV.