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- Development of co-delivery nanoparticles of temozolomide and plasmid DNA for glioblastoma treatmentPublication . Afonso, Inês Sofia Patricio; Costa, Diana Rita Barata; Sousa, Ângela Maria Almeida de; Santos, Adriana Oliveira dosGene therapy is a promising and innovative strategy for cancer treatment, particularly for glioblastoma, an aggressive and highly lethal form of brain cancer with limited therapeutic options and a poor prognosis. Combining gene therapy with chemotherapy has the potential to amplify therapeutic effects through their synergistic interaction, offering a more effective approach to overcoming tumor resistance and improving patient outcomes. This study focused on the development of a co-delivery system based on BSA-coated TMZ-WRAP5/p53 nanocomplexes targeting glioblastoma cells. Temozolomide, a standard chemotherapeutic agent for glioblastoma, was associated with a plasmid encoding the p53 tumor suppressor gene. BSA coating was used to increase the stability, biocompatibility and delivery efficiency of the complexes. An Experimental Design tool was used to optimize the formulation of this complex, including the N/P ratio, BSA concentration and addition time. The optimization process involved evaluating key properties such as particle size, surface charge and DNA complexation capacity. It was determined that the ideal formulation had an (N/P) ratio of 1.03 and a BSA concentration of 0.08%, resulting in complexes of approximately 182 nm, a zeta potential of +9.8 mV and a DNA complexation efficiency of 96.5%. These BSAcoated spherical complexes showed high stability and biocompatibility. In vitro biocompatibility and cytotoxicity studies using MTT showed a substantial reduction in the viability of glioblastoma cells, without toxicity to astrocytes. The results of PCR and qPCR assays showed a significant increase in p53 levels in glioblastoma cells treated with the BSA-coated complex. These data show that this delivery system has significant potential to overcome the challenges associated with conventional glioblastoma therapies.