Blood-brain barrier penetrating nanosystems enable synergistic therapy of glioblastoma

Glioblastoma multiforme (GBM) is a highly malignant and formidable central nervous system tumor that lacks effective therapeutic options. Various characteristics of GBM contribute to this plight, which include inter-/extra- tumor heterogeneity, the presence of the blood brain barrier and GBM stem cells. Standard clinical therapy of GBM has multiple limitations including poor efficacy reflecting, in part, the development of multidrug resistance and unexpected side effects. In addressing these challenges, combination therapies have emerged as promising front-runners and nanotechnology, with its rapid advancements and unique advantages, offers the potential to further improve synergistic combination therapies for GBM. In this review, we outline proof-of-concept studies showcasing recent advances in nanosystem-mediated combinational GBM therapies, with an emphasis on the amplified therapeutic effects of monomodal and multimodal synergistic treatments. The examples detailed in this review provide valuable insights to further understand key paradigms of GBM combinational treatment, inspiring researchers not only in the development of multifunctional nanosystems for brain drug delivery, but also in the design of more rational and effective GBM combination therapies.