Impact of Protein Corona Formation on the Efficacy of Gold Nanoparticles in Breast

Nanotechnology revolutionized the landscape of medical research, particularly in the realm of cancer therapy. Gold nanoparticles (AuNPs), due to their unique properties such as biocompatibility and ease of functionalization, emerged as promising tools for drug delivery. However, once introduced into the biological environment, nanoparticles acquired a protein corona (PC), a layer of proteins adsorbed onto their surface, which significantly altered their behavior, biodistribution, cellular uptake, and therapeutic efficacy. This thesis investigated the impact of protein corona formation on the interaction of gold nanospheres (GNPs) and gold nanostars (GNSs) with the breast cancer cell line SK-BR-3 (HER2+). The primary objective of this research was to elucidate the effects of protein corona formation on the physicochemical properties of GNPs and GNSs and their subsequent impact on cytotoxicity and uptake efficiency in SK-BR-3 cells. The protein corona was formed by incubating AuNPs in a cell culture medium supplemented with 10% fetal bovine serum, and its formation was analyzed through changes in optical properties, surface charge, and size. Through a series of meticulously designed experiments, we explored how the incubation time and conditions influenced the formation of the PC and how these changes affected the interaction between nanoparticles and cancer cells. Methodologically, the study employed a combination of UV-vis spectroscopy, dynamic light scattering (DLS), zeta potential measurements, transmission electron microscopy (TEM) to characterize the PC formation around the two types of AuNPs, microarray analysis and cell viability assay (MTT assay), inductively coupled plasma mass spectrometry (ICP-MS) to assess the impact of the presence PC around the AuNPs on cell viability and cellular uptake. Key findings revealed that the formation of a protein corona on GNPs and GNSs significantly influenced their hydrodynamic diameter and surface charge. These alterations, in turn, affected the nanoparticles' cellular internalization and cytotoxicity, highlighting the critical role of protein-nanoparticle interactions in designing effective nanotherapeutics. The study concluded with insights into the potential clinical applications of these findings and recommendations for future research directions. This research not only advanced our understanding of the nano-bio interface but also provided valuable guidance for the development of more effective nanoparticle-based therapies for breast cancer treatment.