Carboplatin Co-loaded 5-Fluorouracil Nanoparticles Conjugated with Trastuzumab for Targeted Therapy in HER2+ Heterogeneity Breast Cancer

Abstract

Breast cancer, the second-most common cause of cancer-related deaths among women, remains a significant global health challenge. This study focuses on developing trastuzumab (TmAb)-functionalized chitosan nanoparticles (CS-NPs) co-loaded with carboplatin and 5-fluorouracil (5-FU) for targeted treatment of HER2-positive breast cancer. The NPs were prepared via the ionic gelation method, optimized using Design of Experimentation (DoE), and characterized for particle size, zeta potential, PDI, and entrapment efficiency. TmAb conjugation was achieved using NHS and EDC, and further characterization included TEM, syringeability, hemolytic toxicity, in-vitro release, ex-vivo cell line study, and in-vivo anti-cancer activity using the Ehrlich ascites carcinoma (EAC) model. The in-vitro release studies indicated enhanced drug release at pH 5.5 over 32 h and showed first-order kinetics. The TmAb-conjugated NPs demonstrated specificity and targeting in the SK-BR-3 cell line and significant anti-cancer activity in the EAC model, with the highest tumor inhibition rate of 85.19% compared to 58.12% for the drug solution. These findings highlight the potential of TmAb-conjugated NPs for targeted breast cancer therapy, offering improved drug delivery and therapeutic efficacy, paving the way for future clinical applications to reduce side effects and overcome the limitations of conventional chemotherapy.

Graphical Abstract