Nanoplatforms of Pegylated Gold Nanorods Loaded with Non-Steroidal Anti-Inflammatory Drugs: Delivery and Biological Evaluation

This study explored the potential of gold nanorods (AuNRs) functionalized with polyethylene glycol (PEG) and loaded with non-steroidal anti-inflammatory drugs (NSAIDs) fenamic acid (fenH) or its bromo-derivative (4′BrfenH) for targeted drug delivery and preclinical cancer research, given their pH-dependent drug-release profiles and in vitro cytotoxicity in breast cancer cell models. Both formulations demonstrated strong π–π stacking interactions with calf-thymus DNA, suggesting intercalation, and exhibited significant binding affinity to bovine and human serum albumins. Drug release was markedly higher at alkaline pH. As the fenamates are weak acids that are practically insoluble in their neutral form, this pH dependence is attributed principally to the ionization and solubility of the released drug rather than to a responsive carrier. Cytotoxicity assays revealed that AuNRs@PEG@4′BrfenH significantly reduced cell viability in both aggressive (MDA-MB-231) and less metastatic (MCF-7) breast cancer cell lines, particularly at higher concentrations, and caused structural disorganization in 3D spheroid cultures. These findings highlight the promise of AuNRs@PEG@4′BrfenH as a nanoplatform showing pH-dependent release and significant in vitro anticancer activity in breast cancer cell lines and spheroids, supporting its further investigation in relevant tumor models.