In silico optimization of cancer therapies with multiple types of nanoparticles applied at different times

Tsompanas, Michail Antisthenis; Bull, Larry; Adamatzky, Andrew; Balaz, Igor

Abstract

© 2020 The Author(s) 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.

• Journal Article Type: Article
• Acceptance Date: Dec 1, 2020
• Publication Date: 2020-12
• Deposit Date: Jan 12, 2021
• Publicly Available Date: Feb 26, 2021
• Journal: Computer Methods and Programs in Biomedicine
• Print ISSN: 0169-2607
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 200
• Article Number: 105886
• DOI: https://doi.org/10.1016/j.cmpb.2020.105886
• Keywords: Software; Health Informatics; Computer Science Applications
• Public URL: https://uwe-repository.worktribe.com/output/6982267
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0169260720317193