|EphA2 Targeted Doxorubicin Stealth Liposomes as a Therapy System for Choroidal Neovascularization in Rats|
|Wang, Jia-lin1; Liu, Yu-ling1; Li, Ying1; Dai, Wen-bing2; Guo, Zhao-ming2; Wang, Zhao-hui2; Zhang, Qiang2|
|刊名||INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE|
|WOS标题词||Science & Technology|
|关键词[WOS]||RECEPTOR TYROSINE KINASE ; INDUCED ANGIOGENESIS ; PHARMACOKINETICS ; MICROSPHERES ; ADRIAMYCIN ; DELIVERY ; TISSUES ; LIGAND ; GROWTH|
PURPOSE. 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 mu g 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. (Invest Ophthalmol Vis Sci. 2012; 53: 7348-7357) DOI:10.1167/iovs.12-9955
|项目编号||81130059 ; 2009CB930300 ; 2009ZX09310-001|
|资助机构||National Science Foundation ; Ministry of Science and Technology of China|
|作者单位||1.Peking Univ, Hosp 3, Ctr Eye, Beijing 100191, Peoples R China|
2.Peking Univ, Sch Pharmaceut Sci, Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
|Wang, Jia-lin,Liu, Yu-ling,Li, Ying,et al. EphA2 Targeted Doxorubicin Stealth Liposomes as a Therapy System for Choroidal Neovascularization in Rats[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2012,53(11):7348-7357.|
|APA||Wang, Jia-lin.,Liu, Yu-ling.,Li, Ying.,Dai, Wen-bing.,Guo, Zhao-ming.,...&Zhang, Qiang.(2012).EphA2 Targeted Doxorubicin Stealth Liposomes as a Therapy System for Choroidal Neovascularization in Rats.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,53(11),7348-7357.|
|MLA||Wang, Jia-lin,et al."EphA2 Targeted Doxorubicin Stealth Liposomes as a Therapy System for Choroidal Neovascularization in Rats".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 53.11(2012):7348-7357.|