Artificial Enzymes Improve Immunotherapy Treatments
Artificial nanoenzymes have shown promise in improving both the selectivity and efficacy of immunotherapy treatment.
Only a small proportion of patients see the benefits of immunotherapy as tumour cells can employ a multitude of disguises to avoid detection by the immune system. Too ensure more patients can experience the benefits of immunotherapy, new technologies are being developed to help the immune cells identify tumour cells.
One such example is synthetic enzymes that can selectively target tumour cells. Nanoparticle enzymes, or nanoenzymes, have structures completely different from natural enzymes, but can act on the same substrates. Synthetic enzymes are also cheaper to produce which makes them a promising option for clinical treatments.
In this study, the nanoenzymes are designed to mimic the enzymes glutathione oxidase and peroxidase. The substrate is glutathione, an antioxidant that is found at significantly higher concentrations in tumour cells compared to normal body cells. The nanoenzymes are therefore selectively targeted towards the tumour cells. By breaking down glutathione, the nanoenzymes increase the oxidative stress of the tumour cells, significantly disrupting their function.
The activity of the nanoenzymes can be increased further by exposure to near infrared light at wavelengths 1000 and 1350 nm. The enzymes can absorb these light wavelengths, which cause their local environment to heat up and their enzyme activity to increase. The light irradiation can also be applied directly to the tumour, further improving the selectivity of the treatment.
When tumour cells and tumour mice models were treated with immunotherapy and nanoenzymes, the cancer cells displayed increased oxidative stress which led to cell death. The tumour was unable to effectively supress the immune response, as more inflammatory molecules were released which recruited higher number of T-cells to the tumour site.
Once the immune system is able to respond to a tumour, the cells can learn to recognise the tumour cells. The immune system can therefore rapidly launch a response if the tumour resurges.