具有异质脉管系统的肿瘤中纳米药物分布的数值模拟
Numerical modeling of nanodrug distribution in tumors with heterogeneous vasculature.
作者信息
Chou Cheng-Ying, Chang Wan-I, Horng Tzyy-Leng, Lin Win-Li
机构信息
Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan.
Department of Applied Mathematics, Feng Chia University, Taichung, Taiwan.
出版信息
PLoS One. 2017 Dec 29;12(12):e0189802. doi: 10.1371/journal.pone.0189802. eCollection 2017.
The distribution and accumulation of nanoparticle dosage in a tumor are important in evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues.
纳米颗粒剂量在肿瘤中的分布和积累对于评估癌症治疗效果至关重要。细胞存活率可以量化治疗效果,多次治疗后的存活率有助于评估化疗方案的疗效。我们基于描述流体流动和颗粒传输的控制方程建立了一个数学肿瘤模型,以研究肿瘤中的药物传输并计算由此产生的累积浓度。基于累积浓度计算细胞存活率。该模型应用于具有异质血管分布的皮下肿瘤。分别选择了各种大小的葡聚糖和阿霉素作为纳米药物载体和传统化疗药物进行比较。结果表明:1)在当前模拟中,最大的纳米颗粒药物在血管良好区域产生的累积浓度最高,但在周围正常组织中最低,这意味着它对肿瘤具有最佳治疗效果,同时对正常组织几乎没有危害;2)相反,分子化疗药物在血管良好的肿瘤区域产生的累积浓度第二低,但在周围正常组织中最高;3)所有药物在肿瘤坏死区域的累积浓度都非常小,在该区域药物仅通过扩散传输。这可能意味着很难杀死隐藏在其中的肿瘤干细胞。当前模型表明,抗肿瘤药物递送的有效性取决于血管密度和纳米颗粒大小的相互作用,这决定了药物传输特性。由于纳米颗粒对肿瘤细胞具有高治疗效率且对正常组织损伤较小,因此将其用作抗肿瘤药物载体通常比分子化疗药物是更好的选择。