Peking University Eye Center, Peking University Third Hospital, Beijing, People's Republic of China.
Invest Ophthalmol Vis Sci. 2012 Oct 23;53(11):7348-57. doi: 10.1167/iovs.12-9955.
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.
为了提高 RPE 细胞对药物的摄取，增强对脉络膜新生血管（CNV）的疗效，降低药物毒性，通过与同源肽 YSA 缀合，开发了一种 EphA2 靶向的载多柔比星（DOX）的纳米载体。
YSA 与聚乙二醇化脂质偶联。然后，制备并表征了 YSA 修饰的 DOX 隐形脂质体（YSA-SSL-DOX）。评估了它们在人 RPE 细胞系（ARPE-19）中的摄取。在玻璃体内注射后，在激光诱导的大鼠模型中评估了它们对 CNV 的疗效。最后，进行 TUNEL 试验和大鼠视网膜形态观察。
所制备的 YSA-SSL-DOX 的粒径约为 110nm，DOX 的包封效率超过 95%。YSA-SSL-DOX 中 DOX 的泄漏非常缓慢。证实了 EphA2 在 CNV 上的表达。流式细胞术和共聚焦显微镜研究均表明，YSA-SSL-DOX 可促进脂质体 DOX 进入 ARPE-19 细胞的摄取。与未修饰的脂质体 DOX 和生理盐水相比，YSA-SSL-DOX（2.5μg DOX）治疗可显著减少大鼠 CNV 面积（P<0.05）。YSA-SSL-DOX 对大鼠视网膜无明显毒性。
EphA2 靶向隐形脂质体可能是一种有效的视网膜血管生成相关疾病的递药和治疗系统。
