Understanding the Connection between Nanoparticle Uptake and Cancer Treatment Efficacy using Mathematical Modeling.
Understanding the Connection between Nanoparticle Uptake and Cancer Treatment Efficacy using Mathematical Modeling.
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DOI：
10.1038/s41598-018-25878-8
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发表时间：
2018-05-24
影响因子：
4.6
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Brocato TA;Coker EN;Durfee PN;Lin YS;Townson J;Wyckoff EF;Cristini V;Brinker CJ;Wang Z
纳米颗粒在提高癌症治疗功效同时降低毒性和治疗副作用方面显示出巨大的前景。通过测量纳米颗粒生物分布来预测纳米颗粒系统的治疗结果一直具有挑战性，这是由于纳米颗粒相对于游离药物分布通常不匹配的异质分布。我们在这里提出了一个概念验证的研究，使用数学建模与实验来解决这一挑战。用纳米颗粒递送的或游离的多柔比星治疗患有4T1乳腺癌的个体小鼠，结果表明与游离多柔比星相比，负载多柔比星的纳米颗粒的癌症杀伤功效提高。然后，我们开发了一种数学理论，根据石墨炉原子吸收法测定的纳米颗粒生物分布来进行模型预测。模型分析发现，随着肿瘤内纳米颗粒积累的增加，治疗效果呈指数级增加，强调了开发新方法以优化纳米颗粒向肿瘤微环境的递送效率的重要性。
Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been challenging due to the commonly unmatched, heterogeneous distribution of nanoparticles relative to free drug distribution. We here present a proof-of-concept study that uses mathematical modeling together with experimentation to address this challenge. Individual mice with 4T1 breast cancer were treated with either nanoparticle-delivered or free doxorubicin, with results demonstrating improved cancer kill efficacy of doxorubicin loaded nanoparticles in comparison to free doxorubicin. We then developed a mathematical theory to render model predictions from measured nanoparticle biodistribution, as determined using graphite furnace atomic absorption. Model analysis finds that treatment efficacy increased exponentially with increased nanoparticle accumulation within the tumor, emphasizing the significance of developing new ways to optimize the delivery efficiency of nanoparticles to the tumor microenvironment.
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影响因子：
4.9
作者：
Chen F;Nayak TR;Goel S;Valdovinos HF;Hong H;Theuer CP;Barnhart TE;Cai W
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