Abstract

Glioblastoma multiforme (GBM) is a prevalent and highly aggressive type of brain tumour that frequently occurs in older individuals. Radiotherapy solely offers palliative relief; however, it has been observed that chemotherapeutic drugs are only beneficial in enhancing the quality of life in GBM patients with minimal impact on the mortality rate. Moreover, only a limited drug therapy is available for the treatment of GBM, which is the primary reason for the global burden of mortality over the years. Chemotherapeutic agents primarily fail to reach the brain and tumor site due to the presence of the blood-brain tumor barrier (BBTB)/blood-brain barrier (BBB), which prevents access to the tumor microenvironment. Moreover, other factors such as high tumor recurrence, drug resistance, and treatment costs further worsen the management of GBM. Thus, optimizing the existing drug therapy to improve its biopharmaceutical performance has been seen as an alternative approach for GBM treatment. Smart nanomedicines, including liposomes, nanomicelles, polymeric and lipidic nanoparticles, nanomaterials, and nanocomposites, are constituted of biomimetic lipids and biocompatible polymers, which have demonstrated excellent drug loading ability to cross the BBB and BBTB for GBM treatment. Surface modification of nanocarriers with ligands (e.g., folate, lectin, transferrin, glutamate), growth factors, functional peptides, and monoclonal antibodies has significantly improved their potential for targeting drugs and nucleic acids as RNAi therapy for GBM. Moreover, recent innovations in drug therapies, such as the incorporation of theragnostic agents into nanocarriers and antibody-drug conjugates, have provided new insights into the treatment and diagnosis of glioma. This keynote review presents recent advances in therapeutic interventions for GBM, with special emphasis on nanotherapeutic systems to achieve maximal therapeutic benefits.