α_vβ_3整合素受体靶向性超顺磁性脂质体的建立及体外磁共振观察

Development of α_vβ_3 integrin targeted superparamagnetic liposome and in vitro MR observation

目的合成以RGD短肽为亲和成分的靶向性超顺磁性长循环脂质体,并通过体外细胞学实验确定其受体靶向性,探讨其用于肿瘤受体成像的可能性。方法采用薄膜法分别合成表面连接和不连接RGD的靶向性和非靶向性长循环脂质体;以流式细胞分析及共聚焦激光扫描显微镜观察靶向对比剂对HUVEC细胞的特异性标记。结果①合成的超顺磁性脂质体粒径在150nm左右,具有较高的弛豫率;②靶向性对比剂对αvβ3整合素受体具有较高的特异性亲和力;可通过受体介导的内吞作用进入细胞内;③靶向对比剂与细胞结合后,可以明显降低细胞的信号。结论RGD—超顺磁性长循环脂质体具有较高的弛豫率,能与αvβ3整合素受体特异性结合,在靶点特异性浓聚,并能经MR扫描证实。

Objective To synthesize the targeted superparamagnetic liposome with RGD oligopeptide as main binding components, and to assess its targeted ability and possibility of its application in receptor imaging with in vitro fluorescence mi croscopy. Methods SPIO liposomes conjugated with or without Arg-Gly-Asp （RGD） peptides were made by film method. The binding and uptake of RGD-liposomes by HUVECs were analyzed with flow cytometry and confocal laser scanning mi croscopy （CLSM）. Results （1）The superparamagnetic liposome had high relaxation rate with the size of about 150 nm; （2） Targeted contrast medium had specific affinity for αvβ3 integrin and could enter cells with receptor-mediated endocytosis; （3） Cell signal reduced significantly when targeted contrast medium combined with cells. Conclusion The RGD targeted superparamagnetic liposome has high relaxation rate. It can bind particularly with αvβ3 integrins and be detected with in vitro MR imaging.