The Potential of Chronotherapy and Nanotherapy-Based Strategies for Glioblastoma Treatment

Glioblastoma is the most common and aggressive brain tumour in adults, and despite ongoing efforts, effective treatment remains limited. Standard therapies often face challenges because of the tumour's specific biology, its aggressive nature, and the presence of certain physiological barriers in the brain that impede chemotherapeutics from reaching their target. Emerging research in circadian biology highlights the role of the internal circadian clock in tumour progression and treatment response. Evidence suggests that aligning therapy to patients' chronotypes could potentially improve treatment outcomes. At the same time, advances in nanotechnology-including functionalized nanoparticles for drug and/or gene delivery-show promising results while reducing side effects. Additionally, evolving and prominent artificial intelligence tools may significantly contribute to progress in the design of next-generation personalised therapies. This review provides a unique and integrative perspective by examining the hurdles in treating GB and exploring innovative strategies, such as the integration of nanotechnology into chronotherapy protocols, to enhance therapeutic efficacy. The Chronobiology-Nanotechnology combination could not only improve GB patients' survival rates but also lead to a more effective and less toxic personalised approach, distinguishing this work from previous reviews.