# Utilizing Ni(II) complex for metal drug-gel particles in cervical cancer treatment and designing novel drugs through machine learning methods

## TL;DR

A new nickel-based coordination polymer is developed for drug delivery in cervical cancer, with machine learning suggesting improved drug designs for ovarian cancer.

## Contribution

A novel Ni(II) coordination polymer and paclitaxel-loaded metal gel are synthesized, and machine learning is used to design new drugs with better biological activity.

## Key findings

- A Ni(II) coordination polymer [Ni(L)(D-CAM)(H2O)]n was successfully synthesized using a mixed ligand method.
- A HA/CMCS hydrogel with a macroporous structure was prepared and used as a drug carrier for paclitaxel.
- Machine learning simulations suggest novel drugs with low affinity energy and strong interaction with protein receptors for ovarian cancer.

## Abstract

In the present study, a novel coordination polymer (CP) based on Ni(II), namely, [Ni(L)(D-CAM)(H2O)]n (1) (H2D-CAM = (1R,3S)-1,2,2-trimethylcyclopentane-1,3-dicarboxylic acid and L = 3,6-bis(benzimidazol-1-yl)pyridazine), has been produced successfully through applying a mixed ligand synthesis method via reacting Ni(NO3)2·6H2O with 3,6-bis(benzimidazol-1-yl)pyridazine ligand in the presence of a carboxylic acid co-ligand. Hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) are representatives of natural polysaccharides and have good biocompatibility. Based on the chemical synthesis method, HA/CMCS hydrogel was successfully prepared. SEM showed that the lyophilized gel presented a typical macroporous structure with three-dimensional connected pores, which had unique advantages as a drug carrier. Using paclitaxel as a drug model, we further synthesized a novel paclitaxel-loaded metal gel and evaluated its therapeutic effect on cervical cancer. Finally, novel drugs from the reinforcement learning simulation are suggested to have better biological activity against ovarian cancer due to low affinity energy and stronger interaction strength towards the protein receptor.