Executive Summary : | Triple negative breast cancers (TNBCs) are a group of breast cancers that do not express any of the HER-2, estrogen, or progesterone receptors found in hormonal receptor positive and HER-2 positive breast cancers. These cancers make up about 15% of all breast cancers, 70% in individuals with germline BRCA-1 mutations, and 20% in BRCA-2 mutation carriers. TNBCs are immunohistochemically defined by a lack of expression of these receptors, leading to biological aggressiveness, poor prognosis, and a lack of a therapeutic target. Chemotherapy is the main treatment for TNBCs, but it can exacerbate tumor heterogeneity, leading to tumor replacement, metastases, and drug resistance. Over the past few decades, efforts have been made to refine chemotherapy regimens and explore new site-specific therapies, such as endocrine therapy and HER-2 targets like trastuzumab and lapatinib, which have improved patient survival. However, these therapies have not been effective against some resistant types of cancers. The present research project aims to investigate the cancer targeting potential of TKI inhibitor-loaded multifunctional nano formulations for effective breast cancer treatment. The project will design, optimize, develop, and evaluate these nanoparticles for enhanced anti-cancer therapeutic efficacy. specific aims include elucidating the targeting and controlled release pattern, developing the nanoparticles using quality by design and design of experimentation approaches, and exploring the anti-cancer targeting therapeutic potential of the developed nano-formulation through in-vitro cell culture experiments and pre-clinical studies. |