Advances and Challenges in Nano-Delivery Systems for Glioblastoma Treatment: A Comprehensive Review.

Authors: Wang K, Sun J, Zhao H, Wang F, Zhang X, Zhao X, Li Z, Zhang L, Ren H, Guo B

Glioblastoma is the most aggressive and lethal primary brain tumor in adults, with current treatment options offering only limited improvement in patient survival. Despite the advancement of modalities such as immunotherapy, targeted therapy, gene therapy, focused ultrasound, and tumor-treating fields, therapeutic efficacy remains unsatisfactory due to challenges such as the blood-brain barrier, tumor heterogeneity, and treatment resistance. Nanotechnology has emerged as a promising platform to enhance the delivery, specificity, and combinatorial potential of these therapies. By enabling precise and multifunctional delivery of therapeutic agents, nanoscale systems hold the potential to overcome critical biological and pharmacological barriers in glioblastoma treatment. This review provides an overview of recent progress in nanomedicine-based strategies for glioblastoma, critically examines the key challenges that limit their clinical translation, and highlights innovative approaches designed to improve therapeutic outcomes. Future perspectives on how nanotechnology may reshape the landscape of brain tumor treatment are also discussed.

Introduction

Purpose Drug delivery WITHOUT BBB opening

Study Objective To review recent nanomedicine-based strategies for glioblastoma, analyze barriers to clinical translation—particularly blood–brain barrier traversal—and highlight innovative approaches and future directions to improve therapeutic outcomes.

Disease model Glioblastoma

Outcomes and Safety

Summary of Outcomes Nanoparticle-based approaches improve blood–brain barrier penetration, tumor-targeted delivery and multimodal therapeutic efficacy (chemotherapy, gene silencing, immune modulation and photo/radio-sensitization) in glioblastoma models, but translation is limited by biosafety, immunogenicity, tumor heterogeneity and manufacturability challenges.

Duration of biological effect 10 years

Safety-related matter The review highlights concerns about the long-term biosafety and immunogenicity of nanosystems and states that safety, delivery practicality, and regulatory considerations must be addressed to enable clinical translation.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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