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Review Open Access

Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review)

  • Authors:
    • Jing-Xing Si
    • Zheng-Chuang Liu
    • Fang Gu
    • Xiaoli Jin
    • Ying-Yu Ma
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China, Department of Paediatrics, Center for Reproductive Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
    Copyright: © Si et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 83
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    Published online on: August 19, 2025
       https://doi.org/10.3892/ijo.2025.5789
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Abstract

Brain tumors, particularly gliomas, are among the most lethal malignancies, with high mortality driven by a delayed diagnosis and limited therapeutic efficacy. A central challenge lies in the presence of the blood‑brain barrier (BBB), which severely impedes the delivery of systemically administered therapeutics to tumor sites. Addressing this clinical urgency, nanoparticle (NP)‑based delivery systems have emerged as a transformative strategy to enhance brain‑specific drug accumulation, minimize off‑target toxicity and improve treatment outcomes. The present review systematically examined the recent advances in nanocarrier technologies for targeted brain tumor therapy, including liposomes, solid lipid NPs, dendrimers, polymeric nanoplatforms and inorganic nanomaterials. The design principles, mechanisms for BBB traversal, therapeutic payload compatibility and tumor‑targeting capabilities of NP technologies demonstrated in preclinical models have also been highlighted. In addition to drug delivery, emerging applications of nanocarriers in gene therapy were explored and the impact of protein corona formation on NP behavior in vivo was discussed. Finally, current translational bottlenecks were identified and future design considerations to achieve clinically viable, precision‑targeted nanomedicines for brain tumors were outlined.
View Figures

Figure 1

Structural and transport features of
the BBB. (A) Overview of the brain capillaries and the
neurovascular unit, including endothelial cells, pericytes and
astrocyte end-feet. (B) Tight junctions formed by claudins,
occludin and ZO-1 limit paracellular diffusion. (C) The main BBB
transport pathways include transcellular diffusion, paracellular
transport, receptor-mediated and adsorptive transcytosis, efflux by
ABC transporters and influx via solute carrier proteins. This
figure was created in BioRender (paid version; https://www.biorender.com/). BBB, blood-brain
barrier; ZO-1, zonula occludens-1; Ang-2, angiopoietin-2.

Figure 2

General structure of PC and
nanoparticles with PC across the BBB in brain tumors. The chemical
structure of PC and the dynamics of its configuration depend on the
affinity of proteins to the functional groups located on the
surface of NPs and the concentration of protein. High affinity
coated proteins form 'hard' corona, while low affinity coated
proteins form 'soft' corona. The BBB is selective and restrictive
to a variety of molecules. Endothelial cells and the basement
membrane, together with strong lateral tight junctions, further
impede its permeability. This figure was created in BioRender (paid
version; https://www.biorender.com/). BBB,
blood-brain barrier; NP, nanoparticle; PC, protein corona.
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Copy and paste a formatted citation
Spandidos Publications style
Si J, Liu Z, Gu F, Jin X and Ma Y: Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review). Int J Oncol 67: 83, 2025.
APA
Si, J., Liu, Z., Gu, F., Jin, X., & Ma, Y. (2025). Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review). International Journal of Oncology, 67, 83. https://doi.org/10.3892/ijo.2025.5789
MLA
Si, J., Liu, Z., Gu, F., Jin, X., Ma, Y."Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review)". International Journal of Oncology 67.4 (2025): 83.
Chicago
Si, J., Liu, Z., Gu, F., Jin, X., Ma, Y."Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review)". International Journal of Oncology 67, no. 4 (2025): 83. https://doi.org/10.3892/ijo.2025.5789
Copy and paste a formatted citation
x
Spandidos Publications style
Si J, Liu Z, Gu F, Jin X and Ma Y: Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review). Int J Oncol 67: 83, 2025.
APA
Si, J., Liu, Z., Gu, F., Jin, X., & Ma, Y. (2025). Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review). International Journal of Oncology, 67, 83. https://doi.org/10.3892/ijo.2025.5789
MLA
Si, J., Liu, Z., Gu, F., Jin, X., Ma, Y."Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review)". International Journal of Oncology 67.4 (2025): 83.
Chicago
Si, J., Liu, Z., Gu, F., Jin, X., Ma, Y."Nanoparticle‑based delivery systems for targeted therapy in brain tumors: Progress, challenges and perspectives (Review)". International Journal of Oncology 67, no. 4 (2025): 83. https://doi.org/10.3892/ijo.2025.5789
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