Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent implications for rational therapy of restenosis
Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent implications for rational therapy of restenosis
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DOI：
10.1161/01.cir.0000044020.27990.32
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发表时间：
2002-11-26
期刊：
影响因子：
37.8
通讯作者：
Wickline, SA
中科院分区：
文献类型：
--
作者：
Lanza, GM;Yu, X;Wickline, SA
背景-再狭窄是冠状动脉成形术的严重并发症，涉及血管平滑肌细胞（VSMC）从中膜向内膜的增殖和迁移、细胞外基质的合成和重塑。我们以前已经证明，组织因子靶向纳米粒子可以渗透和绑定牵张激活的血管平滑肌中的媒体后，球囊损伤。在本研究中，血管平滑肌细胞为目标的纳米粒子作为药物输送平台，用于预防血管成形术后再狭窄的概念studied.Methods和结果-组织因子靶向的纳米粒子含有阿霉素或紫杉醇在0，0.2，或2.0摩尔%的外脂质层的目标为30分钟的血管平滑肌细胞，并显着抑制其增殖在未来3天的文化。将纳米颗粒靶向VSMC表面表位显著增加了纳米颗粒的抗增殖有效性，特别是对于紫杉醇。体外溶出研究表明，纳米颗粒药物释放持续超过一周。靶向抗增殖结果取决于药物的疏水性和与其他表面活性剂组分的非共价相互作用。用4.7T高分辨率T-1加权MRI显示粘附于VSMC的纳米颗粒的分子成像。MRI F-19光谱的纳米粒子核心提供了一个可量化的方法，为非侵入性剂量的靶向药物payloads. Conclusions，这些数据表明，有针对性的顺磁性纳米粒子可以提供一种新的，MRI可视化，和可量化的药物输送系统，用于预防血管成形术后再狭窄。
Background-Restenosis is a serious complication of coronary angioplasty that involves the proliferation and migration of vascular smooth muscle cells (VSMCs) from the media to the intima, synthesis of extracellular matrix, and remodeling. We have previously demonstrated that tissue factor-targeted nanoparticles can penetrate and bind stretch-activated vascular smooth muscles in the media after balloon injury. In the present study, the concept of VSMC-targeted nanoparticles as a drug-delivery platform for the prevention of restenosis after angioplasty is studied.Methods and Results-Tissue factor-targeted nanoparticles containing doxorubicin or paclitaxel at 0, 0.2, or 2.0 mole% of the outer lipid layer were targeted for 30 minutes to VSMCs and significantly inhibited their proliferation in culture over the next 3 days. Targeting of the nanoparticles to VSMC surface epitopes significantly increased nanoparticle antiproliferative effectiveness, particularly for paclitaxel. In vitro dissolution studies revealed that nanoparticle drug release persisted over one week. Targeted antiproliferative results were dependent on the hydrophobic nature of the drug and noncovalent interactions with other surfactant components. Molecular imaging of nanoparticles adherent to the VSMC was demonstrated with high-resolution T-1-weighted MRI at 4.7T. MRI F-19 spectroscopy of the nanoparticle core provided a quantifiable approach for noninvasive dosimetry of targeted drug payloads.Conclusions-These data suggest that targeted paramagnetic nanoparticles may provide a novel, MRI-visualizable, and quantifiable drug delivery system for the prevention of restenosis after angioplasty.