EVOLUTIONARY APPROACHES TO CANCER NANOTHERAPIES

To change the paradigm of cancer therapy, specifically nanotherapies, is the main goal of EVO-NANO, a consortium of 7 partner institutions working towards creating a pipeline of technologies that will simulate, synthesize, and test new nanotherapies for cancer.

In cancer therapy many hundreds or thousands of candidates are tested up in clinical trials but they never reach the market due to difficulties in translating them to being safe for human use. By taking advantage of Artificial Intelligence in the candidate selection process, EVO-NANO hopes to determine suitability far earlier in the trial stage and prevent costly investment in candidates that ultimately would not reach the market.

EVO-NANO brings together expertise in computer science, artificial evolution, modelling, microfluidics, and medicine and it strongly benefits of the complementary expertise within its consortium composed by research partners, namely universities and hospitals, and one industrial partner.

The project’s workflow involves taking a simulation of a cancer microenvironment with millions of cells (University of Novi Sad) and combining this with a simulated flow profile of how particles move from a blood vessel to interact with the tumour cells (University of Bristol). This is run many times in a parallel computing environment (Åbo Akademi University) and applies evolutionary algorithms to the particle properties (University of the West of England) to find the ideal candidates for tumour penetration and drug delivery. Currently, hundreds of tumours have been simulated in an agent-based model created by EVO-NANO principal investigator.

Each of these simulations compares to the ones that came beforehand, changing certain parameters and conditions to determine whether it outperforms its predecessor, or ‘evolves’.  This method allows the simulation to progress towards the optimal outcome with each run. Additionally, EVO-NANO also simulates molecular mechanics in solution to show what percentage of a surface-bound drug on a nanoparticle interacts with a cancer cell upon contact, which allows to determine the effective dosage of a nanomedicine.

From this evolved simulation, EVO-NANO moves into the synthesis of the relevant particles thanks to its industrial supplier partner (ProChimia) who provides custom synthesis for the output of the simulation. This brought to the synthesis of multiple sizes of gold nanoparticles with attached fluorescent tags for tracing through a biological system and attached numerous novel anti-cancer drugs to create testable nanomedicines based on joint data from the project’s simulations and hospital partners.

These particles can then be applied to in vitro testing in EVO-NANO proposed tumour-on-chip models (IMDEA) that contain a mixture of cancerous cells and cancer stem cells, the latter being a major player in metastasis. The project has currently achieved the production of curved microfluidic channels that closely resemble the rounded architecture of blood vessels, meaning it is now possible to apply a realistic model of nanomedicines exiting a blood vessel into surrounding tumour tissue.

Finally, when these particles are vetted for in vivo testing, they can be applied to live models for final testing with EVO-NANO hospital partners (Vall d’Hebron Research Institute) who can move from murine models to human testing. Therapeutic data for the initial run of drug candidates on cancerous tumours have been obtained, and feed into the pipeline for nanoparticle synthesis for required dosages. Ultimately, each stage of the pipeline feeds back into improving the evolutionary algorithms and simulations, which will mean the longer it runs the more accurate and effective it will become.

Photo by Sharon McCutcheon on Unsplash.

Disclaimer: This story was originally developed as part of the FETFX project, the predecessor of our current initiative.