Vascular Targeting of Radiolabeled Liposomes with Bio-Orthogonally Conjugated Ligands: Single Chain Fragments Provide Higher Specificity than Antibodies.
Vascular Targeting of Radiolabeled Liposomes with Bio-Orthogonally Conjugated Ligands: Single Chain Fragments Provide Higher Specificity than Antibodies.
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DOI：
10.1021/acs.bioconjchem.8b00564
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发表时间：
2018-11-21
影响因子：
4.7
通讯作者：
Muzykantov VR
中科院分区：
文献类型：
--
作者：
Hood ED;Greineder CF;Shuvaeva T;Walsh L;Villa CH;Muzykantov VR
脂质体是一种经过验证的、多功能且临床可行的技术平台，用于血管输送药物和成像探针。尽管靶向脂质体具有推进这些应用的潜力，但复杂的配方以及对最佳亲和配体和缀合策略的需求对其翻译提出了挑战。在此，我们采用无铜点击化学功能化脂质体，通过缀合可点击单克隆抗体（Ab）或其单链可变片段（scFv）来靶向血小板内皮细胞粘附分子（PECAM-1）和细胞内粘附分子（ICAM-1）。为了进行直接定量示踪，脂质体与 111In 进行表面螯合，放射化学产率和纯度 >90%。在体内表征了颗粒大小和分布、稳定性、配体表面密度以及与靶细胞的特异性结合。使用器官中的同位素检测和非侵入性成像（单光子发射计算机断层扫描/计算机断层扫描，SPECT/CT）对小鼠体内静脉注射后脂质体的生物分布进行表征。多达 20-25% 的注射剂量的脂质体携带 PECAM 和 ICAM 配体，但没有对照 IgG 在肺脉管系统中积聚。 scFv/脂质体对PECAM-1和ICAM-1的肺部靶向免疫特异性分别比Ab/脂质体高10倍和2.5倍。因此，最佳配体、良性缀合和标记的组合产生可用于高效和特异性血管靶向的脂质体制剂。
Liposomes are a proven, versatile, and clinically viable technology platform for vascular delivery of drugs and imaging probes. Although targeted liposomes have the potential to advance these applications, complex formulations and the need for optimal affinity ligands and conjugation strategies challenge their translation. Herein, we employed copper-free click chemistry functionalized liposomes to target platelet-endothelial cell adhesion molecule (PECAM-1) and intracellular adhesion molecule (ICAM-1) by conjugating clickable monoclonal antibodies (Ab) or their single chain variable fragments (scFv). For direct, quantitative tracing, liposomes were surface chelated with 111In to a >90% radiochemical yield and purity. Particle size and distribution, stability, ligand surface density, and specific binding to target cells were characterized in vivo. Biodistribution of liposomes after IV injection was characterized in mice using isotope detection in organs and by noninvasive imaging (single-photon emission computed tomography/computed tomography, SPECT/CT). As much as 20–25% of injected dose of liposomes carrying PECAM and ICAM ligands, but not control IgG accumulated in the pulmonary vasculature. The immunospecificity of pulmonary targeting of scFv/liposomes to PECAM-1 and ICAM-1, respectively, was 10-fold and 2.5-fold higher than of Ab/liposomes. Therefore, the combination of optimal ligands, benign conjugation, and labeling yields liposomal formulations that may be used for highly effective and specific vascular targeting.
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影响因子：
46.2
作者：
Jewett JC;Bertozzi CR
通讯作者：
Bertozzi CR
影响因子：
17.1
作者：
Howard, Melissa;Zern, Blaine J.;Anselmo, Aaron C.;Shuvaev, Vladimir V.;Mitragotri, Samir;Muzykantov, Vladimir
通讯作者：
Muzykantov, Vladimir
影响因子：
4.7
作者：
Bak, Martin;Jolck, Rasmus I.;Andresen, Thomas L.
通讯作者：
Andresen, Thomas L.
影响因子：
4.7
作者：
Agarwal, Paresh;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.
DOI：
10.2217/nnm.11.92
发表时间：
2011-09
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Hood E;Simone E;Wattamwar P;Dziubla T;Muzykantov V
通讯作者：
Muzykantov V