Abstract

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%.

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