Jul 2026· NUST Journal of Natural Sciences· Vol 11, pp. 93-126· 0 citations
TL;DR
This review critically explore a diverse variety of advanced nanocarrier platforms designed for anti-proliferative, radiosensitizing and immunomodulatory interventions and highlights how rational nanoparticle design can shift GBM management toward targeted, multimodal precision therapy, offering renewed hope against one of oncology's most intractable diseases.
Abstract
Glioblastoma (GBM) remains one of the most lethal brain malignancies, characterized by aggressive invasion, therapeutic resistance and poor prognosis. Conventional treatment approaches are limited by systemic toxicity, poor blood–brain barrier (BBB) penetration and lack of tumor specificity. Nanoparticle-based therapeutics offer a transformative paradigm redefining drug delivery, diagnostics and multimodal strategies in GBM. In this review, we critically explore a diverse variety of advanced nanocarrier platforms designed for anti-proliferative, radiosensitizing and immunomodulatory interventions. These systems enhance BBB penetration, tumor localization and enable co-delivery of chemotherapeutics, gene therapies and imaging agents with high precision. Innovative approaches show efficacy against glioma stem cells, modulate the tumor microenvironment and address resistance mechanisms. Integration with radiotherapy and immunotherapy yields synergistic tumor suppression and immune activation, advancing personalized nanomedicine. Despite these advancements, translational hurdles remain nanogenotoxicity, long-term biosafety, immune responses and regulatory barriers. This review emphasizes such challenges while identifying opportunities for strategic innovation in GBM nanotherapy. By uniquely bridging preclinical advances with emerging clinical perspectives, we highlight its distinct contribution within the field. By bridging nanotechnology, molecular oncology and bioengineering, we highlight how rational nanoparticle design can shift GBM management toward targeted, multimodal precision therapy, offering renewed hope against one of oncology’s most intractable diseases.
Keywords: Glioblastoma, Nanoparticles, Blood-Brain Barrier, Nanotechnology, Nanomedicine, Nanotherapeutics.
This review systematically summarizes recent advances in nanomedicine enabled GBM therapy from four interrelated perspectives: the optimization of nanomaterial properties, the development of goal-oriented targeting strategies, the rationalization of delivery routes, and the engineering of smart stimuli-responsive nano-systems.
Yu Guo, Keqiang Lu, Wenmiao Luo et al.· Wiley Interdisciplinary Revi...· 1 citation
Glioblastoma remains one of the most lethal brain malignancies, characterized by aggressive proliferation and
high recurrence rates despite multimodal treatment approaches. While paclitaxel demonstrates potent anticancer
activity, its clinical utility in glioblastoma management is severely hampered by its inability to cross the bloodbrain barrier, coupled with poor aqueous solubility and P-glycoprotein-mediated efflux. Current standard care,
based on surgical resection combined with radiotherapy and chemotherapy, yields disappointing median survival
rates of only 12-15 months, underscoring the urgent need for innovative therapeutic strategies. Nanotechnologybased drug delivery systems have emerged as a promising approach to circumvent these limitations. Polymeric
nanoparticles, including PLGA, PLA, PCL, and chitosan-based formulations, can effectively encapsulate
paclitaxel while protecting it from efflux mechanisms and enhancing cellular uptake through receptor-mediated
pathways. Surface functionalization strategies such as PEGylation, peptide conjugation, and targeting ligand
attachment significantly improve blood-brain barrier penetration and tumor-specific accumulation. Despite
promising preclinical results demonstrating substantial improvements in brain drug concentrations and tumor
growth suppression, several obstacles persist in advancing these systems to clinical practice. These include
manufacturing scalability, formulation stability, regulatory requirements, and standardization of quality control
parameters. Furthermore, tumor heterogeneity and variable receptor expression patterns necessitate personalized
therapeutic approaches. This review highlights recent progress in BBB-targeted paclitaxel nanoparticle systems,
outlines key technological advances, addresses current limitations, and identifies future research priorities
essential for successful clinical translation in glioblastoma therapy.
Preeti Sah, Pratik Patel, Rikita Patel et al.· International Journal of Dru...· 0 citations
The findings support the therapeutic potential of exosome-based platforms while also highlighting major challenges, including inconsistencies in isolation protocols, limited cargo- loading capacity, targeting specificity, and in vivo stability.
Shatrudhan Prajapati, Shikha Yadav· Current Neurovascular Resear...· 0 citations
Glioblastoma (GBM) is the most aggressive primary malignancy of the central nervous system. Chimeric antigen receptor T (CAR-T) cell therapy has shown promising therapeutic potential against GBM, yet its efficacy remains constrained by multiple barriers, including physical barriers imposed by the blood-brain barrier and extracellular matrix, the immunosuppressive tumor microenvironment, spatiotemporal antigen heterogeneity, and safety concerns. In this review, we summarize the major obstacles limiting CAR-T therapy in GBM and discuss emerging strategies to overcome these challenges. Next-generation engineered CAR-T cells-through armored modifications, logic-gated regulation, and dual-targeting approaches-enhance specificity, persistence, and controllability. Concurrently, combinatorial approaches leveraging biomaterials enable localized delivery and sustained release of CAR-T cells, while physical modalities, such as focused ultrasound and thermal modulation, can transiently disrupt the blood-brain barrier or induce immunogenic cell death. Integration with real-time imaging further enables dynamic monitoring of therapeutic responses. Together, these synergistic strategies may enhance antitumor efficacy while minimizing systemic toxicity, paving the way for future CAR-T-based therapies in glioblastoma.
Lin Chen, Z. Zou· Critical reviews in oncology...· 0 citations
This review discusses current nanotechnology-based immunotherapies and highlights the emerging role of integrating AI in vaccine development as next-generation strategies for improving outcomes in brain cancer treatment.
Alia Syazana Mohd Roslei, H. Huri, D. A. Pratama et al.· Journal of the Egyptian Nati...· 0 citations
Glioma is one of the most invasive tumors in the central nervous system. Traditional treatment is limited by the blood‐brain barrier and tumor drug resistance, and the prognosis of patients is very poor. At present, there is a lack of a comprehensive review that can systematically integrate various nanotechnology strategies to meet these challenges. This review first analyzes the brain biological barrier and glioma microenvironment that nanoparticles delivery must overcome. Furthermore, the key strategies for crossing these barriers, such as receptor‐mediated transport and physical assistance methods, are systematically reviewed. This paper focuses on the design and characteristics of various nano‐platforms (including inorganic, organic and biological nanoparticles), and discusses in detail how they can drive multimodal synergistic therapies such as chemotherapy, radiotherapy and immunotherapy to improve the curative effect and overcome drug resistance. The purpose of this paper is to provide an integrated perspective for researchers in the field to overcome the delivery barrier and realize innovative therapy by nanotechnology, and to provide a theoretical framework and design ideas for promoting the clinical transformation of the next generation of intelligent and personalized nano‐drugs for glioma.
Wenqian Jiang, Jing Fei, Rangrang Fan et al.· MedComm - Oncology· 0 citations
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