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      EphA2 targeted doxorubicin stealth liposomes as a therapy system for choroidal neovascularization in rats.

      Investigative ophthalmology & visual science

      Animals, Antibiotics, Antineoplastic, administration & dosage, Apoptosis, Cells, Cultured, Choroidal Neovascularization, drug therapy, pathology, Disease Models, Animal, Doxorubicin, analogs & derivatives, Drug Carriers, Flow Cytometry, Humans, In Situ Nick-End Labeling, Liposomes, Male, Microscopy, Confocal, Polyethylene Glycols, Rats, Receptor, EphA2, metabolism

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          To enhance drug uptake in RPE cells, improve efficacy for choroidal neovascularization (CNV), and reduce drug toxicity, an EphA2-targeted nanocarrier loaded with doxorubicin (DOX) was developed by conjugation with a homing peptide YSA. The YSA was coupled to PEGylated lipid. Then, YSA-modified DOX stealth liposomes (YSA-SSL-DOX) were prepared and characterized. Their uptake in a human RPE cell line (ARPE-19) was evaluated. After intravitreous injection, their efficacy against CNV was assessed in a laser-induced rat model. Finally, TUNEL test and morphology observation on rat retina were conducted. The prepared YSA-SSL-DOX was approximately 110 nm in particle size, with an encapsulation efficiency of DOX more than 95%. The leakage of DOX from YSA-SSL-DOX was very slow. The expression of EphA2 on the CNV was confirmed. Both flow cytometry and confocal microscopy studies revealed that YSA-SSL-DOX could facilitate the uptake of liposomal DOX into ARPE-19 cells. Treatment with YSA-SSL-DOX (2.5 μg DOX) resulted in a significant reduction in the CNV area of rats compared with the unmodified liposomal DOX and normal saline (P < 0.05). No obvious toxicity of YSA-SSL-DOX on rat retina was found. EphA2-targeted stealth liposomes might be an effective delivery and therapy system for angiogenesis-related diseases in the retina.

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