Nanoparticle-based drug delivery systems to modulate tumor immune response for glioblastoma treatment

Abstract

Glioblastoma (GBM) is a primary central nervous system neoplasm, characterized by a grim prognosis and low survival rates. This unfavorable therapeutic outcome is partially attributed to the inadequate immune infiltration and an immunosuppressive microenvironment, which compromises the effectiveness of conventional radiotherapy and chemotherapy. To this end, precise modulation of cellular dynamics in the immune system has emerged as a promising approach for therapeutic intervention. The advent of nanoparticle-based therapies has revolutionized cancer treatment and provided highly effective options. Consequently, various strategically designed nano-delivery platforms have been established to promote the efficacy of immune therapy against GBM. This review delves into the recent advancements in nano-based delivery systems that are designed to modulate immune cells in GBM microenvironment, and explores their multifaceted mechanisms, including the blockade of immune checkpoints, the restraint of immunosuppressive cells, the coordination of tumor-associated macrophages, the activation of innate immune cells, and the stimulation of adaptive immunity. Collectively, this summary not only advances the comprehension involved in modulating antitumor immune responses in GBM, but also paves the way for the development of innovative therapeutic strategies to conquer GBM.

Statement of significance

Glioblastoma (GBM) is the most lethal brain tumor, with a median survival rate of merely 12–16 months after diagnosis. Despite surgical, radiation and chemotherapy treatments, the two-year survival rate for GBM patients is less than 10 %. The treatment of GBM is challenging mainly because several issues associated with the GBM microenvironment have not yet been resolved. Most recently, novel drug delivery approaches, based on the clear understanding of the intrinsic properties of GBM, have shown promise in overcoming some of the obstacles. In particular, taking account of the highly immunosuppressive tumor microenvironment in GBM, recent advancements in nano-based delivery systems are put forward to stimulate immune cells in GBM and unravel their multifaceted mechanisms. This review summarizes the latest nanoparticle-based drug delivery systems to modulate tumor immune response for glioblastoma treatment. Moreover, the development trends and challenges of nanoparticle-based drug delivery systems in modulating the immunity of GBM are predicted, which may facilitate widespread regimens springing up for successfully treating GBM.