Intravitreal delivery of the cationic micelle DMP suppressed the development of choroidal neovascularization

Age-related macular degeneration (AMD)-associated choroidal neovascularization (CNV) causes severe vision loss. This study evaluated the therapeutic potential of cationic DMP micelles for CNV. DMP micelles were synthesized by modifying PEG-PCL with DOTAP, to form self-assembled nanoparticles. Cytotoxicity was assessed in 661w and human Müller cells via the MTT assay. BN rats with laser-induced CNV received intravitreal DMP or saline. CNV severity was evaluated via fundus fluorescein angiography (FFA) and IB4-stained neovascular area quantification. Retinal transcriptomes were analyzed by RNA-seq. Cellular uptake mechanisms were studied via the use of endocytosis inhibitors (chlorpromazine, methyl-β-cyclodextrin, filipin III). Endothelial migration was tested via a scratch assay. DMP micelles exhibited favorable properties (86.48 nm, +46.4 mV) and low cytotoxicity (IC50 >300 mg/mL vs PEI25K). DMP significantly reduced the FFA leakage score (1.2±0.4 vs saline 2.5±0.6, p<0.01) and IB4+ area (35,602±5,412 vs 58,341±7,203 μm², p<0.001). RNA-seq revealed upregulated antigen presenting genes (RT1-Da, RT1-Ba, RT1-Db1, RT1-Bb) and the immune modulator Slpi. Cellular uptake involved clathrin- and lipid raft-mediated endocytosis. DMP inhibited endothelial migration in vitro. DMP micelles demonstrate dual antiangiogenic and immune-modulating effects in CNV models with retinal biocompatibility. The ability of DMP to suppress neovascularization and activate antigen presentation pathways highlights their therapeutic potential for wet AMD.