摘要
目的构建一种以肿瘤新生血管为靶向的顺磁性长循环纳米脂质体,并探讨其靶向肿瘤的能力。方法设计并采用FMOC(fluorenylmethyloxycarbonyl,FMOC)固相合成法合成RGD10肽(GARYCRGD-CFDG)-赖氨酸-甘氨酸-甘氨酸(lysine-glycine-glycine,KGG臂)-棕榈酸(Pal)复合物;采用薄膜超声分散法制备包封MRI(magnetic resonance lmaging,MRI)造影剂GD-DTPA(Gadopentetate Dimeglumine)的血管靶向顺磁性长循环纳米脂质体(neovessel-targeted PEGylated Gadopentetate Dimeglumine liposomes,T-PEG-GD-LP)和普通顺磁性长循环纳米脂质体(PEGylated Gadopentetate Dimeglumine liposomes,PEG-GD-LP),采用激光粒度分析仪和透射电子显微镜进行形貌表征测定,超滤离心法测定其包封率,MRI扫描测定其信号强度;为验证T-PEG-GD-LP与肿瘤组织的特异性亲和力,检测了HUVEC、A549细胞对其的摄取能力。结果透射电子显微镜显示T-PEG-GD-LP、PEG-GD-LP均呈规则的圆形或略呈椭圆形,粒径检测结果显示其平均粒径小于100nm,MRI测定T-PEG-GD-LP信号强度介于GD-DTPA与PEG-GD-LP之间,HU-VEC、A549两种细胞对T-PEG-GD-LP的摄取量均高于GD-DTPA和PEG-GD-LP(P<0.05)。结论构建的肿瘤新生血管靶向顺磁性长循环纳米脂质体具有良好的肿瘤靶向能力,可成为一种新型有效的肿瘤靶向MRI造影剂。
Objective To develop neovessel-targeted PEGylated paramagnetic liposomes and investigate their potential value as a tumor specific magnetic resonance imaging（MRI） contrast agent.Methods Using Fmoc solid-phase synthesis chemistry to design and synthesis GARYCRGDCFDG-KGG-palmitic acid conjugate.Neovessel-targeted paramagnetic liposomes were prepared by the thin film dispersion sonication method.Morphology of liposomes was observed by transmission electron microscope（TEM）.Mean particle size and particle size distribution of PEGylated liposomes were determined by laser particle sizing analysis.Entrapped efficiency of Gd-DPTA was determined by centrifugal ultrafiltration.The signal intensity of targeted paramagnetic liposomes was evaluated by MRI.To evaluate the affinity between targeted liposomes and tumor cells or vessel endothelial cells,the cellular uptake experiments were performed to study the effect of the receptor-mediated endocytosis.Results The image of TEM showed that both the non-targeted and targeted PEGylated liposomes were of discrete and round structure with size smaller than 100nm,which were consistent with the results obtained from the particle size measurement.Entrapped efficiency of the prepared paramagnetic liposomes was from 45.5to 52.0%.The signal intensity of neovessel-targeted paramagnetic PEGylated liposomes was between Gd-DTPA and non-targeted PEGylated liposomes.Neovessel-targeted paramagnetic PEGylated liposomes showed higher cellular uptake than the non-targeted liposomes in both cell lines.Conclusion New formulation of neovessel-targeted PEGylated paramagnetic liposomes might be potential tumor-specific MRI contrast agents.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2010年第11期1215-1218,共4页
Cancer Research on Prevention and Treatment
基金
国家高技术研究发展计划资助项目(2008AA02Z442)
上海市科委纳米专项基金资助项目(0752nm018)
