title: EphA2 targeted doxorubicin stealth liposomes as a therapy system for choroidal neovascularization in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  EphA2-targeted stealth liposomes might be an effective delivery and therapy system for angiogenesis-related diseases in the retina.
authors.affiliation: Peking University Eye Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Jia-lin
authors.initials: JL
authors.lastname: Wang
authors.forename: Yu-ling
authors.initials: YL
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Wen-bing
authors.initials: WB
authors.lastname: Dai
authors.forename: Zhao-ming
authors.initials: ZM
authors.lastname: Guo
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D017209:Apoptosis; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004337:Drug Carriers; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008081:Liposomes; D008297:Male; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D036104:Receptor, EphA2 / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D036104:Receptor, EphA2