Nanotechnology-based immunotherapy: integrating Artificial Intelligence (AI) with current strategies in combating brain cancer disease

Abstract Brain cancer is one of the most challenging malignancies and a major contributor to worldwide morbidity and mortality. Glioblastoma, the most aggressive adult brain tumor, is associated with poor prognosis despite conventional therapies such as surgery, chemotherapy, and radiotherapy, which often result in severe toxicity and long-term side effects. Immunotherapy holds the potential to provide durable and specific anti-tumor responses; however, its success in brain cancer is hindered by obstacles such as the blood-brain barrier, immunosuppressive tumor microenvironment, and tumor heterogeneity. Nanomedicine offers a powerful approach to overcoming these barriers through targeted and efficient drug delivery. Nanotechnology-based platforms, including lipid-based, polymeric, and inorganic nanoparticles, have demonstrated superior therapeutic efficacy compared to free drugs, with several formulations advancing into clinical trials. Among these, nanotechnology-enabled vaccines represent an emerging frontier, capable of enhancing antigen presentation, stimulating strong immune responses, and overcoming tumor-induced immunosuppression. By combining the precision of nanocarriers with the long-lasting protection of vaccines, nano-vaccines hold great potential to transform brain cancer immunotherapy. Recent studies also suggest that integrating artificial intelligence (AI) with nanotechnology could further enhance the design, targeting, and effectiveness of immunotherapies. Moreover, AI is revolutionizing treatment development by enabling the prediction of immunogenicity, immune responses, and optimizing formulation design and dosing strategies. These advancements collectively accelerate the development and enhance the precision and efficiency of immunotherapy. Hence, this review discusses current nanotechnology-based immunotherapies and highlights the emerging role of integrating AI in vaccine development as next-generation strategies for improving outcomes in brain cancer treatment.