Despite their great promise, only a few nanoparticle formulations have been approved for clinical use in oncology. The failure of nano-scale drugs to enhance cancer therapy is in large part due to inefficient delivery. To overcome this outstanding problem, a better understanding of how the physical properties (i.e., size, surface chemistry, and shape) of nanoparticles affect their transvascular transport in tumors is required. In this study, we developed a mathematical model for nanoparticle delivery to solid tumors taking into account electrostatic interactions between the particles and the negatively-charged pores of the vessel wall. The model predictions suggest that electrostatic repulsion has a minor effect on the transvascular transport of nanoparticles. On the contrary, electrostatic attraction, caused even by small cationic charges (surface charge density less than 3 × 10−3 C/m2) can lead to a twofold or more increase in the transvascular flux of nanoparticles into the tumor interstitial space. Importantly, for every nanoparticle size, there is a value of charge density above which a steep increase in transvascular transport is predicted. Our model provides important guidelines for the optimal design of nanoparticle formulation for delivery to solid tumors.
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机译:尽管前景广阔,但只有少数纳米颗粒制剂被批准用于临床。纳米级药物未能增强癌症治疗的主要原因是给药效率低下。为了克服这个突出的问题,需要更好地理解纳米粒子的物理性质(即,尺寸,表面化学和形状)如何影响其在肿瘤中的经血管运输。在这项研究中,我们考虑到颗粒与血管壁带负电荷的孔之间的静电相互作用,开发了将纳米颗粒递送到实体瘤的数学模型。模型预测表明静电排斥对纳米颗粒的跨血管运输影响较小。相反,即使是很小的阳离子电荷(表面电荷密度小于3×10 -3 sup> C / m 2 sup>)引起的静电引力也可能导致两倍以上的电荷。纳米颗粒的跨血管通量增加进入肿瘤间隙。重要的是,对于每个纳米颗粒大小,都有一个电荷密度值,在该值之上可以预测跨血管运输的急剧增加。我们的模型为纳米颗粒制剂的最佳设计提供了重要的指导,以便将其递送至实体瘤。
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