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In silico optimization of cancer therapies with multiple types of nanoparticles applied at different times.
Computer Methods and Programs in Biomedicine ( IF 4.9 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.cmpb.2020.105886
Michail-Antisthenis Tsompanas , Larry Bull , Andrew Adamatzky , Igor Balaz

Background and Objective: Cancer tumors constitute a complicated environment for conventional anti-cancer treatments to confront, so solutions with higher complexity and, thus, robustness to diverse conditions are required. Alternations in the tumor composition have been documented, as a result of a conventional treatment, making an ensemble of cells drug resistant. Consequently, a possible answer to this problem could be the delivery of the pharmaceutic compound with the assistance of nano-particles (NPs) that modify the delivery characteristics and biodistribution of the therapy. Nonetheless, to tackle the dynamic response of the tumor, a variety of application times of different types of NPs could be a way forward. Methods: The in silico optimization was investigated here, in terms of the design parameters of multiple NPs and their application times. The optimization methodology used an open-source simulator to provide the fitness of each possible treatment. Because the number of different NPs that will achieve the best performance is not known a priori, the evolutionary algorithm utilizes a variable length genome approach, namely a metameric representation and accordingly modified operators. Results: The results highlight the fact that different application times have a significant effect on the robustness of a treatment. Whereas, applying all NPs at earlier time slots and without the ordered sequence unveiled by the optimization process, proved to be less effective. Conclusions: The design and development of a dynamic tool that will navigate through the large search space of possible combinations can provide efficient solutions that prove to be beyond human intuition.



中文翻译:

在计算机上优化在不同时间应用的多种纳米颗粒的癌症治疗方法。

背景与目的:癌症肿瘤构成了常规抗癌治疗面临的复杂环境,因此需要具有更高复杂性的解决方案,因此需要对各种状况的鲁棒性。作为常规治疗的结果,已经证明了肿瘤组成的变化,使细胞整体具有抗药性。因此,该问题的可能答案可能是借助纳米颗粒(NPs)来输送药物化合物,从而改变治疗的输送特性和生物分布。尽管如此,为了应对肿瘤的动态反应,不同类型NP的多种应用时间可能是前进的方向。方法:计算机模拟根据多个NP的设计参数及其应用时间,对优化进行了研究。优化方法使用开源模拟器来提供每种可能治疗方法的适用性。由于先验未知将获得最佳性能的不同NP的数量,因此进化算法利用了可变长度基因组方法,即同分异构表示法和相应的修饰算子。结果:结果突出了这样一个事实,即不同的应用时间对治疗的坚固性具有重要影响。然而,在较早的时隙应用所有NP且未通过优化过程显示有序序列的事实证明效果不佳。结论: 动态工具的设计和开发将在可能的组合的大型搜索空间中导航,可以提供证明超出人类直觉的有效解决方案。

更新日期:2020-12-01
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