用于药物输送的纳米颗粒通常需要静脉注射，使其暴露在脉管系统内的流体力下，但血流对纳米颗粒输送的影响仍不完全清楚。在这里，我们利用转基因斑马鱼胚胎来研究荧光标记的聚乙二醇化脂质体的积累与各种血管生成血管中的各种血流动力学因素（例如流速、壁剪切应力（WSS）和流动模式）之间的关系。我们根据共焦图像重建了血管结构的 3D 模型，并使用计算流体动力学来计算局部 WSS、速度并定义流动模式。随后将荧光标记脂质体的空间分布绘制在同一 3D 空间内，并与局部血流动力学参数相关。通过计算流体动力学和体内实验的结合，我们发现脂质体在 WSS 为 0.1-0.8 Pa 的血管区域积聚，时间平均壁剪切应力与体内脂质体定位之间呈现逆线性相关性 (R2 > 0.85) 。有趣的是，流动模式似乎并不影响脂质体的积累。总的来说，我们的研究结果表明，隐形脂质体具有被动靶向低流量脉管系统的潜力，包括毛细血管和类似于肿瘤血管网络的复杂血管生成脉管系统。© 2024。控释协会。

Nanoparticles used for drug delivery often require intravenous administration exposing them to fluid forces within the vasculature, yet the impact of blood flow on nanoparticle delivery remains incompletely understood. Here, we utilized transgenic zebrafish embryos to investigate the relationship between the accumulation of fluorescently labeled PEGylated liposomes and various hemodynamic factors (such as flow velocity, wall shear stress (WSS), and flow pattern) across a wide range of angiogenic blood vessels. We reconstructed 3D models of vascular structures from confocal images and used computational fluid dynamics to calculate local WSS, velocities, and define flow patterns. The spatial distribution of fluorescently labeled liposomes was subsequently mapped within the same 3D space and correlated with local hemodynamic parameters. Through the integration of computational fluid dynamics and in vivo experimentation, we show that liposomes accumulated in vessel regions with WSS between 0.1-0.8 Pa, displaying an inverse linear correlation (R2 > 0.85) between time-averaged wall shear stress and liposome localization in vivo. Interestingly, flow pattern did not appear to impact liposome accumulation. Collectively, our findings suggest the potential of stealth liposomes for passive targeting of low-flow vasculature, including capillaries and intricate angiogenic vasculature resembling that of tumor vessel networks.© 2024. Controlled Release Society.