Research goals

A recent report published by the World Health Organization in the year 2018 indicates that cancer is responsible for around 9.6 million deaths globally and 0.78 million in India alone. Even after the introduction of several new treatment modalities targeting different pathways, the emergence of drug-resistance and relapse has increased at an alarming rate.

Recent literature from the scientific community, including our lab as well, working in the area of ion transport across biological membranes clearly demonstrates that synthetic ion transporters can kill the cancer cells either by disrupting cellular chloride ion homeostasis or co-transporting HCl owing to their ability to neutralize pH gradients and inhibit autophagy in cells.

Data Source: Globocan 2018

Besides, the acidic microenvironment of tumor tissues resists the cellular uptake of many commonly used weakly basic cancer drugs, which get protonated at lower pH. On that account, chemical substances having the ability to neutralize the pH gradient, such as HCl co-transporters can restore the drug sensitivity synergistically.

Nevertheless, these achievements are beyond any control to make the system target specific. There is a tremendous need to have a spatiotemporal control over the activities of such systems to attain target specificity and thereby rendering their bio-applicability.

To this end, the main focus of my research is to design stimuli-responsive ion transporters that can function only under specific conditions or in the presence of an external stimulus. The idea is to synthesize a series of related transporters and corresponding pro-transporters which can specifically get cleaved in the presence of our desired suitable stimulus leading to the perturbation of cellular ion homeostasis. By and large, focus will be there to compare the viability of cancer and healthy cells in 2D and 3D models followed by a detailed investigation on the pathway of cell death to validate the approach to target cancer.