Guwahati: Scientists from two leading research institutions in Assam have developed a promising “smart” cancer drug that can switch itself on in the presence of conditions commonly found inside cancer cells, potentially offering a more targeted approach than conventional chemotherapy, which can also damage healthy cells.
The research was jointly led by Dr Asis Bala of the Institute of Advanced Study in Science and Technology (IASST), Guwahati, and Dr Krishna P Bhabak of IIT-Guwahati, along with researchers Rahul Kesarwani, Nikita Pal and Dorothy Das.
The study, titled “Rational Development of Activatable Prodrugs of the GSTP1 Inhibitor NBDHEX: Turn-On NIR Fluorogenic Drug Delivery with Selective Anticancer Activity”, was published in the Journal of Medicinal Chemistry.
The drug candidate, RK-251, is a reactive oxygen species (ROS)-responsive “prodrug” designed to deliver NBDHEX, a potent inhibitor of the cancer-associated protein GSTP1.
Unlike conventional chemotherapy drugs that circulate through the body and can affect healthy as well as 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.
The researchers used a specially designed dual positively charged NIR fluorophore, QCy7, to create the prodrug. The approach could allow researchers to track drug activation while delivering the anticancer compound.
Strong activity against aggressive breast cancer
Laboratory experiments 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). This protein is overexpressed in many cancer cells and can help them neutralise 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. Importantly, the embryos showed no noticeable abnormalities or acute toxicity during the study.
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.
For Assam, the research is notable for bringing together scientists from IASST and IIT-Guwahati to develop a drug-delivery approach aimed at one of the major challenges in cancer treatment: targeting tumour cells while limiting damage to healthy tissue.
Also Read: Barely online: Why a Mizoram village is struggling to teach kids