Systems Optimization Lab, Department of Mechanical Engineering, McGill University, Montreal, QC H3A 0G4, Canada.
J Biomech Eng. 2020 Dec 1;142(12). doi: 10.1115/1.4047657.
Nanoparticle-mediated drug delivery may be a promising alternative to traditional chemotherapy of high systemic toxicity. Tumor tissue architecture poses a challenge to delivery of nanoparticles. Small and spherical nanoparticles have poor adherence to the tumor vasculature, while larger and more eccentric ones create high heterogeneity in tissue-to-drug exposure. In previous work, we quantified these tradeoffs using numerical optimization. In this study, we demonstrate that simultaneous delivery of multiple nanoparticle designs can enhance drug distribution in the cancerous tissue without compromising nanoparticle tumoral accumulation. We formulate and solve optimization problems to find the optimal constituent of the heterogeneous injection in terms of nanoparticle design diversity that increases drug distribution by 14%.
纳米颗粒介导的药物输送可能是一种有前途的替代传统高全身毒性化疗的方法。肿瘤组织架构对纳米颗粒的输送构成了挑战。小而球形的纳米颗粒与肿瘤血管系统的黏附性差，而较大和更偏心的纳米颗粒在组织与药物暴露之间造成高度的异质性。在以前的工作中，我们使用数值优化来量化这些权衡。在这项研究中，我们证明了同时输送多种纳米颗粒设计可以在不影响纳米颗粒肿瘤积累的情况下增强药物在癌变组织中的分布。我们提出并解决了优化问题，以找到最佳的异质注射组成部分，即通过增加 14%的药物分布来提高纳米颗粒设计多样性。
