Preclinical Evaluation of Targeted Nanoparticle-Based Drug Delivery in Triple-Negative Breast Cancer
Keywords:
Triple-Negative Breast Cancer (TNBC), Nanoparticle Drug Delivery, Targeted Therapy, Preclinical Study, Doxorubicin, Ligand Functionalization, Tumor Targeting, In Vivo Biodistribution, Chemotherapy, Drug ResistanceAbstract
Triple negative breast cancer (TNBC) is a special subtype of breast cancer that is currently not novelized, i.e. has no estrogen, progesterone and HER2 receptors, and therefore is difficult to be treated as well as has poor clinical outcomes. A preclinical evaluation with such a targeted nanoparticle based drug delivery system is presented in this study to enhance the therapeutic efficacy of TNBC with minimal systemic toxicity. Physicochemical properties of ligand functionalized nanoparticles with the encapsulation of doxorubicin were developed and evaluated for drug release kinetics and cellular uptake are presented. Targeted nanoparticles enhanced killing of TNBC cells versus free drug and non targeted controls in cytotoxicity assays of TNBC cell lines (MDA MB 231). These studies performed in TNBC xenograft mouse models show in vivo biodistribution and therapeutic efficacy with preferntial tumor accumulation and tumor volume reduction. Off target organ toxicity was confirmed and reduced by histopathological analysis. The implications of these findings are the potential of targeted nanoparticle platform for enhancing the therapeutic index of chemotherapeutic agents in TNBC and their potential clinical translation.
