Zhang Hua, Kusunose Jiro, Kheirolomoom Azadeh, Seo Jai W, Qi Jinyi, Watson Katherine D, Lindfors Heather A, Ruoslahti Erkki, Sutcliffe Julie L, Ferrara Katherine W
Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
Biomaterials. 2008 Apr;29(12):1976-88. doi: 10.1016/j.biomaterials.2007.12.033. Epub 2008 Feb 6.
Efficacious delivery of drugs and genes to the heart is an important goal. Here, a radiolabeled peptide-targeted liposome was engineered to bind to the heart, and the biodistribution and pharmacokinetics were determined by dynamic positron emission tomography in the FVB mouse. Efficient targeting occurred only with an exposed ligand and a dense concentration of peptide (6000 peptides/particles). Liposomes targeted with CRPPR or other arginine-rich peptides with an exposed guanidine moiety bound within 100 s after intravenous injection and remained stably bound. With CRPPR-targeted particles, the radioisotope density in the heart averaged 44 +/- 9% injected dose/gram of tissue, more than 30-fold higher than in skeletal muscle. The rapid and efficient targeting of these particles can be exploited in drug and gene delivery systems and with dynamic positron emission tomography provides a model system to optimize targeting of engineered particles.
将药物和基因有效递送至心脏是一个重要目标。在此，构建了一种放射性标记的肽靶向脂质体使其与心脏结合，并通过动态正电子发射断层扫描在FVB小鼠中确定其生物分布和药代动力学。仅在配体暴露且肽浓度高（6000个肽/颗粒）时才会发生有效靶向。用CRPPR或其他带有暴露胍基部分的富含精氨酸的肽靶向的脂质体在静脉注射后100秒内结合，并保持稳定结合。对于CRPPR靶向颗粒，心脏中的放射性同位素密度平均为44±9%注射剂量/克组织，比骨骼肌高30多倍。这些颗粒的快速有效靶向可应用于药物和基因递送系统，并且动态正电子发射断层扫描提供了一个优化工程颗粒靶向的模型系统。
