Surface changes of two-dimensional molybdenum disulphide nanosheets can lead to highly effective applications like delivering drugs to diseased cells, according to a study by the Department of Organic Chemistry (OC) and Materials Research Centre (MRC), Indian Institute of Science (IISc).

Nanomaterials must usually modified or customised depending on the application to improve efficiency. They are chemically modified through functionalisation, which involves attaching ligands (small or large molecules) to the surface of the nanomaterial.

“Thiols can be exchanged with naturally-occurring thiols in biological systems, which could allow drugs attached to these nanosheets to be released. These chemically-modified nanosheets were also found to be safe to use inside living cells,” according to the release shared by IISc. In the new study, the researchers modified the surface of 2D-MoS2 nanosheets with thiol (sulphur-containing) ligands. 

“Our study shows that thiol exchange on 2D-MoS2 nanosheets is effective, and the nanomaterial is stable in the presence of various biomolecules. This is an important observation as it will make this nanomaterial highly beneficial for biomedical applications like drug delivery,” explained Mrinmoy De, Associate Professor at the Department of Organic Chemistry and senior author of the study published in ACS Nano.

To modify the surface of the 2D-MoS2 nanosheets to create a functional version (BOD-MoS2), the team first used a fluorescent thiol called boron-dipyrromethene (BOD-SH). After that, they tested the possibility of thiol-to-thiol exchange on BOD-MoS2 using glutathione (GSH), a naturally occurring thiol found in abundance in cancer cells. “GSH molecules swapped places with BOD-SH on the surface of the nanosheet—a process that they confirmed using fluorescence techniques.”

The researchers attached an anti-cancer drug doxorubicin (DOX) to the nanosheet surface. They found the possibility of thiol exchange between GSH and DOX, allowing DOX to get dropped off at the diseased site. “Because the exchange happens only in the presence of high concentrations of GSH found in diseased cells, drugs like DOX can be delivered specifically to cancer cells without affecting normal cells, which can also potentially reduce any side effects.”

Previous efforts have focused on using gold nanoparticles for such biomedical applications, according to the researchers. Still, these nanoparticles are expensive and have limited efficiency due to their non-selectivity between mono thiols and disulphides.

“Our experiments show that 2D-MoS2 nanosheets can be an effective substitute for gold nanoparticles, and they will be greatly beneficial in the field of nanomedicine,” said Pradipta Behera, a researcher at IISc. Moreover, the MoS2 nanosheets were found to be stable in biofluids. They also have a higher surface area than gold nanoparticles, meaning they can be more efficient. 

Moving forward, the team said it plans to improve nanomaterial’s stability in the presence of various thiol-containing liquids and explore alternative surface modification approaches to customise the nanosheets for other applications. “This work on 2D-MoS2 nanosheets can be developed in the future as an alternative to RNA and DNA delivery applications, which can be useful for detecting and treating infections such as COVID-19,” added Behera.