Vascular deposition patterns for nanoparticles in an inflamed patient-specific arterial tree
Vascular deposition patterns for nanoparticles in an inflamed patient-specific arterial tree
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DOI：
10.1007/s10237-013-0520-1
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发表时间：
2014-06-01
影响因子：
3.5
通讯作者：
Decuzzi, Paolo
中科院分区：
文献类型：
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作者：
Hossain, Shaolie S.;Hughes, Thomas J. R.;Decuzzi, Paolo
炎症是包括癌症和动脉粥样硬化在内的许多疾病的前兆，可诱导特定血管分子的不同表面表达。载有治疗和显像剂的血源性纳米颗粒（NPs）可以识别并利用这些分子作为血管对接点。在这里，在等几何分析框架内开发了一个计算模型，以了解和预测炎症动脉树中NPs的血管沉积。NPs的直径从0.1到m不等，并装饰有针对三种内皮粘附分子的抗体，即血管内细胞粘附分子-1 (ICAM-1)，血管细胞粘附分子-1 （VCAM-1）和e-选择素，其表面密度取决于局部壁剪切应力。结果表明，VCAM-1靶向NPs的粘附效率更高，ICAM-1靶向NPs的粘附效率最低，导致平均颗粒表面密度降低约一个数量级。与VCAM-1（异质性指数1.4）相比，ICAM-1和E-selectin定向的m - NPs在分叉的血管分支上分布更均匀（异质性指数分别为0.9和1.0）。当NPs以相同比例包裹VCAM-1和E-selectin抗体时，与仅针对VCAM-1的靶向颗粒相比，其血管分布更加均匀，从而证明了NP多价性在血管靶向中的优势。此外，与上支相比，较大的NPs (m)在下支粘附更多（200%）。这个计算框架提供了如何操纵大小、配体类型、密度和多价来增强个体患者NP血管粘附的见解。
Inflammation, a precursor to many diseases including cancer and atherosclerosis, induces differential surface expression of specific vascular molecules. Blood-borne nanoparticles (NPs), loaded with therapeutic and imaging agents, can recognize and use these molecules as vascular docking sites. Here, a computational model is developed within the isogeometric analysis framework to understand and predict the vascular deposition of NPs within an inflamed arterial tree. The NPs have a diameter ranging from 0.1 to m and are decorated with antibodies directed toward three endothelial adhesion molecules, namely intravascular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, whose surface density depends on the local wall shear stress. Results indicate VCAM-1 targeted NPs adhere more, with ICAM-1 directed NPs adhering least efficiently, resulting in approximately an order-of-magnitude lower average particle surface density. ICAM-1 and E-selectin directed m NPs are distributed more uniformly (heterogeneity index 0.9 and 1.0, respectively) over the bifurcating vascular branches compared to their VCAM-1 counterparts (heterogeneity index 1.4). When the NPs are coated with antibodies for VCAM-1 and E-selectin in equal proportions, a more uniform vascular distribution is achieved compared with VCAM-1-only targeted particles, thus demonstrating the advantage of NP multivalency in vascular targeting. Furthermore, the larger NPs (m) adhere more ( 200 %) in the lower branches compared to the upper branch. This computational framework provides insights into how size, ligand type, density, and multivalency can be manipulated to enhance NP vascular adhesion in an individual patient.