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Design Optimization of Tumor Vasculature-Bound Nanoparticles.
Scientific Reports 2018 December 12
Nanotherapy may constitute a promising approach to target tumors with anticancer drugs while minimizing systemic toxicity. Computational modeling can enable rapid evaluation of nanoparticle (NP) designs and numerical optimization. Here, an optimization study was performed using an existing tumor model to find NP size and ligand density that maximize tumoral NP accumulation while minimizing tumor size. Optimal NP avidity lies at lower bound of feasible values, suggesting reduced ligand density to prolong NP circulation. For the given set of tumor parameters, optimal NP diameters were 288 nm to maximize NP accumulation and 334 nm to minimize tumor diameter, leading to uniform NP distribution and adequate drug load. Results further show higher dependence of NP biodistribution on the NP design than on tumor morphological parameters. A parametric study with respect to drug potency was performed. The lower the potency of the drug, the bigger the difference is between the maximizer of NP accumulation and the minimizer of tumor size, indicating the existence of a specific drug potency that minimizes the differential between the two optimal solutions. This study shows the feasibility of applying optimization to NP designs to achieve efficacious cancer nanotherapy, and offers a first step towards a quantitative tool to support clinical decision making.
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