In vivo real-time tracking of single quantum dots conjugated with monoclonal anti-HER2 antibody in tumors of mice
In vivo real-time tracking of single quantum dots conjugated with monoclonal anti-HER2 antibody in tumors of mice
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DOI：
10.1158/0008-5472.can-06-1185
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发表时间：
2007-02-01
期刊：
影响因子：
11.2
通讯作者：
Ohuchi, Noriaki
中科院分区：
文献类型：
--
作者：
Tada, Hiroshi;Higuchi, Hideo;Ohuchi, Noriaki
追踪单纳米颗粒的研究为研究活体小鼠体内药物载体的相互作用和转运过程提供了新的见解。在这里，我们报道了使用背侧皮肤折叠室和高灵敏度相机的高速共聚焦显微镜在活小鼠肿瘤中跟踪与肿瘤靶向抗体结合的单粒子量子点（Qdot）。将单克隆抗her2抗体标记的Qdot注射到her2过表达乳腺癌小鼠体内，分析其向肿瘤传递机制的分子过程。通过背侧皮褶腔，可以在30帧/秒的速度下清楚地观察到qdot抗体单个复合物在肿瘤内的运动。我们成功地确定了六个传递过程：最初在血管内的循环中，在外渗期间，在细胞外区域，与细胞膜上的HER2结合，从细胞膜移动到核周区域，以及在核周区域。定量分析了这六个过程，以了解qdot抗体递送的限速约束。复合物在每个阶段的运动都是“走走停停”。单颗粒在体内传递过程的图像分析为抗体偶联治疗性纳米颗粒提供了有价值的信息，这将有助于提高治疗效果。
Studies with tracking of single nanoparticles are providing new insights into the interactions and processes involved in the transport of drug carriers in living mice. Here, we report the tracking of a single particle quantum dot (Qdot) conjugated with tumor-targeting antibody in tumors of living mice using a dorsal skinfold chamber and a high-speed confocal microscope with a high-sensitivity camera. Qdot labeled with the monoclonal anti-HER2 antibody was injected into mice with HER2-overexpressing breast cancer to analyze the molecular processes of its mechanistic delivery to the tumor. Movement of single complexes of the Qdot-antibody could be clearly observed at 30 frames/s inside the tumor through a dorsal skinfold chamber. We successfully identified six processes of delivery: initially in the circulation within a blood vessel, during extravasation, in the extracelullar region, binding to HER2 on the cell membrane, moving from the cell membrane to the perinuclear region, and in the perinuclear region. The six processes were quantitatively analyzed to understand the rate-limiting constraints on Qdot-antibody delivery. The movement of the complexes at each stage was "stop-and-go." The image analysis of the delivery processes of single particles in vivo provides valuable information on antibody-conjugated therapeutic nanoparticles, which will be useful in increasing therapeutic efficacy.