Chemical and biological investigations of new vanadium compounds: determining their potential in the treatment of cancer

Cancer is one of the leading causes of death worldwide, placing a heavy economic burden on healthcare systems and deeply affecting patients and their families. Current cancer treatments often rely on platinum-based drugs such as cisplatin, oxaliplatin, and carboplatin, which are used in around 20% of cases. While these drugs can be effective, they are not specifically targeted to cancer cells, leading to harmful side effects like kidney damage, nerve toxicity, and nausea. Additionally, many cancers eventually become resistant to these treatments, underscoring the need for new drugs that can selectively target and destroy cancer cells without harming healthy tissue. In the early stages of our research, we focused on developing new cancer drugs using vanadium, a metal with potential therapeutic properties. However, vanadium compounds have faced challenges in the past due to poor solubility and instability in water, making it difficult to test their effectiveness. Despite these challenges, we have made progress in improving the design of these drugs, and using advanced techniques, we identified several vanadium-based compounds that show promise for treating cancer. These compounds were able to interact with DNA, increase reactive oxygen species (which can damage cancer cells), and induce cell death. Importantly, they work through different mechanisms than platinum-based drugs, which may help overcome the problem of drug resistance. While our initial results are promising, there are still several challenges to address. The solubility and stability are not optimal for future applications, and we do not yet fully understand how these vanadium compounds are taken up by cells or where they are locating inside the cell, posing issues in determining any specific cellular targets. With renewed funding for this fellowship, we will tackle these issues by focusing on three key objectives: Improving Solubility and Stability: We will refine the chemical properties of the vanadium compounds to ensure they are stable and dissolve effectively in water, making them easier to administer. We will also enhance the delivery of these compounds by attaching them to peptide nanocarriers. These nanocarriers will protect the drugs from premature breakdown and improve their delivery to cancer cells. The nanocarriers will also be engineered to release the drugs specifically in cancerous tissue, increasing their effectiveness while minimising side effects. Optimising Redox Chemistry: Due to differences in oxygen concentrations of cancer cells, and important redox chemistry for targeting cancers which have become resistant, we will improve the redox properties of the compounds to enhance their ability to specifically target cancer cells. Enhancing Cellular Uptake: To ensure the drugs are taken up by the cancer cells, we will incorporate fluorescent markers to track their movement within the cells. Additionally, we will design targeting groups that direct the drugs specifically to mitochondria, the cell's energy centres, where changes in redox balance contribute to drug resistance in cancer cells. This project will be supported by collaborations with experts at the University of Warwick, including those in polymer science, the School of Life Sciences, and the Warwick Medical School. By combining expertise in chemistry, biology, and medicine, we aim to establish a leadership position in the development of vanadium-based drugs for cancer treatment. This research has the potential to significantly improve cancer therapy, offering more targeted treatments that reduce side effects, lower healthcare costs, and ultimately benefit patients worldwide.