Research Projects

Breast cancer (BC) is a major cause of death among women worldwide, including in India. It is typically classified into four molecular subtypes based on the presence or absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Triple Negative Breast Cancer (TNBC), the most lethal subtype, lacks all three receptors and constitutes 15-20% of breast cancer cases. TNBC is highly aggressive, characterized by a high rate of visceral metastasis, early recurrence, and poor prognosis, making it challenging to treat with conventional therapies. Chemotherapy remains the main frontline treatment for TNBC, yet drug resistance and the tumor's immunosuppressive environment limit clinical responses, contributing to poor survival outcomes. Interestingly, TNBC demonstrates higher immunogenicity than other BC types, largely due to the overexpression of immunosuppressive molecules like programmed cell death ligand 1 (PD-L1) and Indoleamine 2,3-dioxygenase (IDO), particularly in advanced stages. This immunogenic profile has positioned immunotherapy (IT) as a promising alternative for TNBC. However, challenges persist due to IT resistance, limited tumor penetration of antibodies, and inability to reach intracellular targets. To mitigate these issues, small molecule inhibitors targeting immunomodulatory pathways, including IDO inhibitors, have been explored as potential strategies to reduce immunosuppression. However, low clinical responses have restricted their success. Nanotechnology, particularly nanogel-based drug delivery systems, has gained attraction as a potential solution. These nanogels offer selective targeting capabilities and therapeutic efficacy. By embedding IDO inhibitors with diselenide linkages, the nanogels can respond to high reactive oxygen species (ROS) and glutathione (GSH) levels, allowing controlled release within the tumor microenvironment. Additional drugs within these nanogels can be bound using acetal, hydrazone, and Schiff base linkages, which enable release in response to acidic conditions typical of tumor cells. These multi-stimuli release mechanism enhances the treatment’s specificity and effectiveness. Post-synthesis, these nanocarriers will undergo rigorous testing to evaluate drug release kinetics, cytotoxicity, and mechanistic impacts in vitro, with the most effective carriers advancing to in vivo studies. The controlled, localized release of combined drugs is anticipated to bolster immune responses and simultaneously target various pathways, potentially improving TNBC treatment outcomes. By enabling controlled drug release in response to the tumor’s specific microenvironment, these nanogels can optimize therapeutic efficacy even at low drug doses. With this innovative approach, nanotechnology may offer significant advancements in breast cancer treatment, particularly for TNBC, by enhancing the potency of anticancer agents and improving patient survival rates.