Towards clinical translation of cancer nanomedicine, it is important to systematically investigate the various parameters related to nanoparticle (NP) physicochemical properties, tumor characteristics, and inter-individual variability that affect the tumor delivery efficiency of therapeutic nanomaterials. Comprehensive investigation of these parameters using traditional experimental approaches is impractical due to the vast parameter space; mathematical models provide a more tractable approach to navigate through such a multidimensional space. To this end, we have developed a predictive mathematical model of whole-body NP pharmacokinetics and their tumor delivery in vivo, and have conducted local and global sensitivity analyses to identify the factors that result in low tumor delivery efficiency and high off-target accumulation of NPs. Our analyses reveal that NP degradation rate, tumor blood viscosity, NP size, tumor vascular fraction, and tumor vascular porosity are the key parameters in governing NP kinetics in the tumor interstitium. The impact of these parameters on tumor delivery efficiency of NPs is discussed, and optimal values for maximizing NP delivery are presented.

对于癌症纳米医学的临床翻译，重要的是系统地研究与纳米颗粒（NP）的理化特性，肿瘤特征和个体间变异性相关的各种参数，这些参数会影响治疗性纳米材料的肿瘤递送效率。由于巨大的参数空间，使用传统的实验方法对这些参数进行全面研究是不切实际的。数学模型提供了一种更易于处理的方法来浏览此类多维空间。为此，我们开发了全身NP药代动力学及其在体内肿瘤递送的预测数学模型，并进行了局部和全局敏感性分析，以找出导致低的肿瘤递送效率和高的脱靶NP积累的因素。我们的分析表明，NP降解速率，肿瘤血液粘度，NP大小，肿瘤血管分数和肿瘤血管孔隙度是控制肿瘤间质NP动力学的关键参数。讨论了这些参数对NPs肿瘤递送效率的影响，并提出了用于最大化NP递送的最佳值。