Nano-drops of Biomimetic Macromolecular Drugs Based on Macrophage Membranes for Targeted Treatment of Fundus Diseases

Ocular fundus diseases—including age-related macular degeneration and diabetic retinopathy—are leading causes of irreversible vision loss worldwide. Current macromolecular therapies require frequent intravitreal injections, which increase patient burden and complication risks. To address these limitations, we engineered a macrophage membrane-biomimetic nanovesicle encapsulating ranibizumab (designated M@R) for noninvasive ocular delivery and selective targeting of inflammatory lesions in the posterior segment. In vitro studies demonstrated that M@R retained potent cytokine-scavenging activity against key pro-inflammatory mediators, and the macrophage membrane coating significantly enhanced transcytosis-mediated transport of ranibizumab across ocular epithelial barriers. Ex vivo and in vivo studies confirmed that M@R is capable of noninvasive traversal of ocular barriers, achieving targeted delivery to inflammatory lesions within the fundus. In a laser-induced choroidal neovascularization (CNV) mouse model, topical ocular administration of M@R significantly reduced both the area and thickness of CNV, attributable to its dual anti-inflammatory and anti-VEGF activities. Although multiple dosing was required to achieve therapeutic efficacy comparable to that of a single intravitreal ranibizumab injection, M@R exhibited markedly improved safety profiles, with no observable local ocular toxicity or systemic adverse effects following repeated administration. Collectively, these findings establish macrophage membrane-coated nanovesicles as a promising platform for barrier-penetrating, inflammation-targeted delivery of biologics in the treatment of fundus diseases.