Investigation of the effects of targeted drug loaded nanoparticles on glioblastoma

Current treatment for glioblastoma, an aggressive primary brain cancer, involves radiotherapy and temozolomide (TMZ). However, due to the development of resistance to TMZ, cancer recurrence, and high mortality rates, there is a need for new therapeutic approaches. In this context, nanoparticles (NPs) may offer novel treatment options. In this study, human serum albumin (HSA) NPs loaded with TMZ (TMZ&NP) were synthesized. To target glioblastoma, NPs were conjugated with folic acid (FA), transferrin (Tf), or atherosclerotic plaque (AP) ligands. The efficacy of the NPs was investigated both in vitro and in vivo in glioblastoma models. TMZ&NPs induced high cytotoxicity in C6 glioma cells depending on the ligand type. TMZ, TMZ&NP, and TMZ&NP-FA inhibited the growth of C6 spheroid diameters. TMZ, TMZ&NPs, and TMZ&NP-AP increased the number of active caspase-3+ cells in spheroids. In an orthotopic rat glioblastoma model, TMZ&NP formulations had a positive effect on body weight gain in glioma groups. According to magnetic resonance imaging (MRI) analysis, TMZ, TMZ&NP, TMZ&NP-FA, TMZ&NP-Tf, and combined treatments reduced tumor size. Relative cerebral blood flow (rCBF) decreased with TMZ&NP, TMZ&NP-Tf, and TMZ&NP-AP treatments. Cellular damage within the tumor increased with TMZ&NP-FA, TMZ&NP-AP, and combined NP treatments. The number of blood vessels in the peritumoral area was reduced by TMZ&NP-FA and TMZ&NP-Tf applications. TMZ&NP, TMZ&NP-FA, and TMZ&NP-Tf reduced VEGF+ cells in the tumor core. Ultrastructural analyses confirmed that NPs were internalized into neurons, glial cells, axons, tumor cells, and structures related to the blood brain barrier (BBB) in the neocortex, hippocampus, corpus callosum, and tumor tissues. In conclusion, this study emphasizes the importance of active targeting systems and shows that NP formulations may be a functional tool in the treatment of glioblastoma. These systems should be investigated in human glioblastoma models and their safety and efficacy should be investigated further.