Scientists from two leading research institutions in Assam, the Institute of Advanced Study in Science and Technology (IASST) and IIT-Guwahati, have jointly developed a promising ‘smart’ cancer drug that can selectively target cancer cells, potentially offering a more targeted approach than conventional chemotherapy.
The research, led by Dr Asis Bala of IASST and Dr Krishna P Bhabak of IIT-Guwahati, along with researchers Rahul Kesarwani, Nikita Pal, and Dorothy Das, has resulted in the development of a drug candidate called RK-251. This reactive oxygen species (ROS)-responsive ‘prodrug’ is designed to deliver NBDHEX, a potent inhibitor of the cancer-associated protein GSTP1.
Unlike conventional chemotherapy drugs that can affect both healthy and cancerous cells, RK-251 is designed to remain inactive until it encounters elevated levels of reactive oxygen species (ROS) - molecules that are often present at higher levels in cancer cells. Once activated, RK-251 rapidly releases NBDHEX and simultaneously produces a near-infrared (NIR) fluorescence signal, effectively providing a ‘turn-on’ indication that the drug has been activated.
Laboratory experiments have found that RK-251 showed potent anticancer activity against MDA-MB-231 cells, a widely used model of triple-negative breast cancer, while showing greater selectivity towards cancer cells than non-malignant cells. The drug works by releasing NBDHEX, which inhibits glutathione-S-transferase pi (GSTP1), a protein overexpressed in many cancer cells that can help them neutralize certain anticancer drugs and survive treatment.
The researchers also observed changes in key cancer-marker genes following treatment with RK-251, providing further evidence of its anticancer activity. The compound was subsequently tested in developing zebrafish embryos, where ROS-triggered activation produced the expected red fluorescence, with no noticeable abnormalities or acute toxicity observed.
The findings suggest that RK-251 could potentially combine targeted drug delivery with real-time fluorescence tracking, although much more research will be needed before the approach can be considered for human treatment.
