The effective dispersion of nanovectors within the tumor microvasculature
The effective dispersion of nanovectors within the tumor microvasculature
复制标题
DOI：
10.1007/s10439-005-9072-6
复制
发表时间：
2006-04-01
影响因子：
3.8
通讯作者：
Netti, PA
中科院分区：
文献类型：
--
作者：
Decuzzi, P;Causa, F;Netti, PA
基于泰勒剪切色散理论，考虑分子和对流扩散的贡献，研究了纳米矢量沿不可渗透和可渗透毛细管的有效纵向扩散。这个问题在用于血管内输送药物和造影剂的纳米载体的运输中非常重要。研究表明，对于给定的毛细血管尺寸和血流动力学条件，存在一个临界半径a(cr)，此时沿毛细血管的有效纵向扩散具有最小值：a<a(cr)的纳米载体主要通过布朗扩散进行扩散，而a>a(cr)的纳米载体主要通过对流进行扩散，有效扩散系数随着a而增长。在可渗透性导管中，与正常无渗漏血管相比，有效扩散显着降低，并且得出a（cr）几乎与血管的水力渗透性L-p线性增长。研究表明，具有最大有效纵向扩散率的血管可以优先成为循环载体的目标。基于这些发现，提出了以下策略来增加针对肿瘤血管的纳米载体的数量：（i）使用具有正常血管临界半径的纳米载体，（ii）注射具有不同半径的纳米载体团注，以及（iii）肿瘤脉管系统的正常化。最后，需要强调的是，载体的大小应根据肿瘤块发生的身体区域以及肿瘤的类型、恶性程度和状态来选择。
The effective longitudinal diffusion of nanovectors along non-permeable and permeable capillaries has been studied considering the contribution of molecular and convective diffusion based on the Taylor's theory of shear dispersion. The problem is of importance in the transport of nanovectors used for the intravascular delivery of drugs and contrast agents.It has been shown that for a given capillary size and hemodynamic conditions a critical radius a(cr) exists for which the effective longitudinal diffusion along the capillary has a minimum: Nanovectors with a < a(cr) diffuse mainly by Brownian diffusion whereas nanovectors with a > a(cr) diffuse mainly by convection and the effective diffusion coefficient grows with a. In permeable conduits, the effective diffusion reduces significantly compared to normal non-leaky vessels and it has been derived that a(cr) grows almost linearly with the hydraulic permeability L-p of blood vessels.It has been shown that the blood conduits with the largest effective longitudinal diffusivity could be preferentially targeted by the circulating vectors. Based on these findings, the following strategies are proposed to increase the number of nanovectors targeting the tumor vessels: (i) The use of nanovectors with a critical radius for normal vessels, (ii) the injecting of bolus of nanovectors with different radii, and (iii) the normalization of the tumor vasculature. Finally, it has been emphasized that the size of the vector should be selected depending on the body district where the tumoral mass is developing and on the type, malignancy, and state of the tumor.