Nanotechnology in brain cancer treatment: The role of gold nanoparticles as therapeutic enhancers

Brain cancer, with glioblastoma (GBM) being one of the most aggressive and treatment-resistant cancers, represents a leading cause of mortality and morbidity worldwide. Its complex nature and the presence of the blood-brain barrier (BBB) significantly hinder the effectiveness of conventional therapies, posing major challenges for treatment development. In this context, nanotechnology—particularly nanomedicine—has emerged as a promising strategy to overcome these barriers and enhance standard treatments like chemotherapy and radiotherapy (RT). This review focuses on three of the most challenging brain neoplasms—GBM, brain metastases, and pediatric brain tumors—and explores the growing role of nanoparticle-based therapies, with special emphasis on gold nanoparticles (AuNPs). Owing to their unique physicochemical properties, such as surface functionalization, biocompatibility, and the ability to cross the BBB, AuNPs have shown great potential in selectively delivering drugs, enhancing RT as radiosensitizers, and reducing systemic toxicity. Despite their therapeutic advantages, concerns remain regarding the long-term safety of AuNPs. Their small size and ability to cross biological barriers may lead to unintended biodistribution, immune responses, and cytotoxic effects. Reported risks include inflammatory reactions, apoptosis, and developmental toxicity, highlighting the need for comprehensive safety assessments. AuNPs offer a promising avenue for improving therapeutic efficacy and patient survival in brain cancers. However, their clinical application requires further in-depth preclinical and clinical evaluation to ensure both effectiveness and safety