Liposomal modular complexes for simultaneous targeted delivery of bioactive gases and therapeutics.
Liposomal modular complexes for simultaneous targeted delivery of bioactive gases and therapeutics.
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DOI：
10.1016/j.jconrel.2009.10.037
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发表时间：
2010-03-19
影响因子：
10.8
通讯作者：
McPherson, David D.
中科院分区：
文献类型：
--
作者：
Klegerman, Melvin E.;Wassler, Michael;Huang, Shao-Ling;Zou, Yuejiao;Kim, Hyunggun;Shelat, Harnath S.;Holland, Christy K.;Geng, Yong-Jian;McPherson, David D.
血管内回声脂质体（ELIP）可适于包封一氧化氮以促进治疗剂向动脉粥样硬化斑块的超声增强递送。然而，靶向ELIP的NO负载导致抗体（Ab）免疫反应性降低93%。测试了以下假设：NO-ELIP和Ab缀合的ELIP的生物素/抗生物素蛋白介导的偶联将使得能够共同递送生物活性气体和ELIP，其可以包封其他试剂而不损失靶向效率。通过向等比例的生物素化Ab-ELIP和NO-ELIP中加入过量的链霉亲和素来引发复合物形成。荧光去卷积显微镜、Coulter Multisizer 3分析和流式细胞术证明ELIP偶联程序在1分钟内形成≥10个脂质体的混合聚集体。血管内超声成像和ELISA显示，回声和靶向效率完全保留，分别为69-99%。当与NO-ELIP复合时，双功能靶向CD 34和ICAM-1的ELIP（BF-ELIP）增加了人单核细胞通过transwell板中人冠状动脉内皮细胞单层的迁移，相对于非特异性IgG-ELIP对照增加了4倍，相对于单独的BF-ELIP增加了2倍。得出的结论是，这种新的多功能缀合方法提供了一个平台技术的位点特异性的共同交付的生物活性气体和其他试剂。
Intrinsically echogenic liposomes (ELIP) can be adapted to encapsulate nitric oxide to facilitate ultrasound-enhanced delivery of therapeutic agents to atherosclerotic plaques. However, the NO loading of targeted ELIP caused a 93% decrease of antibody (Ab) immunoreactivity. The following hypothesis was tested: biotin/avidin-mediated coupling of NO-ELIP and Ab-conjugated ELIP will enable co-delivery of bioactive gases and ELIP that can encapsulate other agents without loss of targeting efficiency. Complex formation was initiated by addition of excess streptavidin to equal proportions of biotinylated Ab-ELIP and NO-ELIP. Fluorescence deconvolution microscopy, Coulter Multisizer 3 analysis and flow cytometry demonstrated that the ELIP coupling procedure formed mixed aggregates of ≥10 liposomes within 1 minute. Intravascular ultrasound imaging and ELISA showed that echogenicity and targeting efficiency were completely and 69–99% retained, respectively. When complexed to NO-ELIP, ELIP bifunctionally targeted to both CD34 and ICAM-1 (BF-ELIP) increased human mononuclear cell migration through human coronary artery endothelial cell monolayers in transwell plates 4-fold relative to a nonspecific IgG-ELIP control and 2-fold relative to BF-ELIP alone. It was concluded that this novel multi-functional conjugation methodology provides a platform technology for site-specific co-delivery of bioactive gases and other agents.
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影响因子：
15.9
作者：
Rudic, RD;Shesely, EG;Sessa, WC
通讯作者：
Sessa, WC
影响因子：
3.4
作者：
Klegerman, Melvin E.;Huang, Shaoling;McPherson, David D.
通讯作者：
McPherson, David D.
DOI：
10.1016/s0735-1097(98)00607-x
发表时间：
1999-03-01
影响因子：
24
作者：
Demos, SM;Alkan-Onyuksel, H;McPherson, DD
通讯作者：
McPherson, DD
影响因子：
3
作者：
Bick, RJ;Poindexter, BJ;Schiess, MC
通讯作者：
Schiess, MC
影响因子：
3.8
作者：
AlkanOnyuksel, H;Demos, SM;McPherson, DD
通讯作者：
McPherson, DD