Research Projects

The tumor metastasis, chemoresistance and tumor relapse have emerged as a major challenge in the treatment of triple negative breast cancer (TNBC). Recently it was discovered that small population of tumor initiating cells called breast cancer stem cells (BCSCs) are responsible for it. Currently available drugs target only tumor cells (non-BCSCs), while sparing BCSCs. Therefore, there is a need for therapeutic agents which target and eliminate both. Notch signaling pathway is a regulatory pathway responsible for angiogenesis in bulk tumor cells (non-BCSCs) and self renewal & maintenance in BCSCs. Inhibition of γ secretase is an attractive strategy to silence notch signaling. However, the clinical application of γsecretase inhibitors is limited due their non-selective toxicity to healthy cells. The purpose of the present study, therefore, is to design an active targeted delivery system for γ-secretase inhibitor, DAPT to achieve radical cure of TNBC.

We have successfully formulated the DAPT loaded SLNs(DAPT@SLNs)and characterised. We have successfully tethered the DR5mAb to the developed DAPT@SLNs and prepared DR5-DAPT@SLNs. We have performed the statistical analysis and published 2 SCI indexed articles. We have studied the pharmacokinetics, biodistribution and biocompatibility of the developed DR5-DAPT@SLNs. The developed formulation DR5-DAPT@SLNs were tested for their efficacy and safety in in vivo breast cancer mice models. The results suggest that the developed formulation had better target-specificity and anti-cancer profile. We have performed the statistical analysis and published 2 SCI indexed articles.