Design maps for nanoparticles targeting the diseased microvasculature
Design maps for nanoparticles targeting the diseased microvasculature
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DOI：
10.1016/j.biomaterials.2007.09.025
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发表时间：
2008-01-01
期刊：
影响因子：
14
通讯作者：
Ferrari, Mauro
中科院分区：
文献类型：
--
作者：
Decuzzi, Paolo;Ferrari, Mauro
全身给药的配体包被的纳米颗粒已被证明在体内识别生物靶标。这可以为疾病的早期检测、成像和治疗提供突破性的解决方案。在心血管应用中，纳米颗粒已被直接靶向到患病的脉管系统，并且这种递送方法甚至在癌症研究中也变得越来越受欢迎，这得到了关于正常脉管系统和肿瘤脉管系统之间的生物学差异的越来越多的证据的支持。这项工作的重点是在整个数学建模的血管靶向纳米粒子的优化设计。这样的纳米颗粒应该被工程化，以便特异性地识别并牢固地粘附到患病的血管壁，承受流体动力学的移位力，并控制内皮细胞的摄取。一个随机的方法来预测纳米粒子的粘附强度下流动的细胞层已经耦合到一个数学模型受体介导的内吞作用的纳米粒子。已经确定了支配这两个事件的主要几何、生物物理和生物参数，并强调了它们的相对重要性。三种不同的状态的颗粒/细胞系统已被预测，即无粘附，粘附与内吞作用和粘附与内吞作用，基于几何和生物物理性质的颗粒和生物条件的网站上的粘附。已经生成设计图以用作初步参考，用于选择作为生理参数的函数的纳米颗粒的性质，如在目标脉管系统内的期望粘附部位处的壁剪切应力和受体表面密度。(C)2007爱思唯尔有限公司版权所有。
Systemically administered ligand-coated nanoparticles have been proved to recognize biological targets in-vivo. This can provide breakthrough solutions for the early detection, imaging and cure of diseases. In cardiovascular applications, nanoparticles have been targeted directly to the diseased vasculature, and such delivery approach is becoming increasingly popular even in cancer research, supported by the growing body of evidences on the biological differences between normal and tumor vasculature. This work focuses on the optimal design of nanoparticles for vascular targeting throughout mathematical modeling. Such nanoparticles should be engineered so as to recognize specifically and adhere firmly to the diseased vessel walls withstanding the hydrodynamic dislodging forces and control uptake by the endothelial cells. A stochastic approach for predicting the adhesion strength of nanoparticles to a cell layer under flow has been coupled to a mathematical model for the receptor-mediated endocytosis of nanoparticles. The main geometrical, biophysical and biological parameters governing both events have been identified and their relative importance highlighted. Three different states for the particle/cell system have been predicted, namely no adhesion, adhesion with no endocytosis and adhesion with endocytosis, based upon the geometrical and biophysical properties of the particle and the biological conditions at the site of adhesion. Design maps have been generated to be used as a preliminary reference for choosing the properties of the nanoparticle as a function of physiological parameters, as the wall shear stress and the receptors surface density, at the site of desired adhesion within the target vasculature. (C) 2007 Elsevier Ltd. All rights reserved.