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.