Research Projects

TNBC is an aggressive subtype of breast cancer characterized by the absence of estrogen (Erα) and progesterone receptors (PR), as well as the human epidermal growth factor receptor gene (HER-2). Till date, existing therapeutic options have primarily focused on targeting TNBC cells; however, targeting TNBC cells with conventional chemotherapeutic medications has been demonstrated to spare TNBC stem cells (TNBCSCs), increasing the risk of tumor relapse and recurrence due to the ability of TNBCSCs to initiate new tumor growth. To address the aforementioned issue, novel strategies for targeting TNBCSCs are being explored. However, targeting TNBCSCs alone, on the other hand, would mean sparing residual normal breast and tumor cells, which could lead to recurrence and relapse due to dedifferentiation of progenitor cells, fused cells, differentiated cells, cancer cells, and cells that have acquired the stemness gene from other cells. A successful strategy for combating TNBC and preventing relapse should, therefore, target both TNBC cells and TNBCSCs at the same time. The role of SP/tNK-1R and COX-2 enzyme in the progression of TNBC is well established. In the current study, we hypothesized that combination of Aprepitant and Etoricoxib has the potential to introduce a new strategy in chemotherapy with superior anti-TNBC potential. However non-specific delivery of Aprepitant and Etoricoxib as bulk drugs can cause serious cardiovascular side effects and milder side effects such as nausea, vomiting, dizziness, headache, Gastrointestinal side effects, skin irritation. During recent times, Polymeric nanoparticles (PNPs) have been extensively investigated as nano drug delivery systems due to their ability to incorporate and co-deliver two or more lipophilic drugs loaded in their core and also due to their characteristic property of flexible surface modification that can deliver site specifically. Poly(lactic-co-glycolic acid) (PLGA) NPs are reported to be biodegradable, biocompatible, non-toxic, and highly stable in biological fluids and during storage. Therefore, development of a nanoformulation surface modified with specific biomarker that can deliver the loaded drugs site specifically to TNBC cells and TNBCSCs can reduce the aforementioned side effects. Engineering the drug-loaded PLGA nanoparticles (PNPs) with TNBC-specific marker like CD44 promotes the TNBC-specific delivery of NP, thereby enhancing the therapeutic efficacy of loaded drugs while minimizing their toxic effects. So, in the present study, we propose to develop PLGA nanoparticles loaded with Aprepitant and Etoricoxib, surface engineered with CD44 for site specific delivery to TNBC cells and TNBCSCs.