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Enhancement of Therapies for Glioblastoma (GBM) Using Nanoparticle-based Delivery Systems

  • Review Article
  • Theme: NIPTE Research and Perspective: Advances in Nanotechnology-Based Drug Delivery
  • Published:
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Abstract

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumor. Current FDA-approved treatments include surgical resection, radiation, and chemotherapy, while hyperthermia, immunotherapy, and most relevantly, nanoparticle (NP)-mediated delivery systems or combinations thereof have shown promise in preclinical studies. Drug-carrying NPs are a promising approach to brain delivery as a result of their potential to facilitate the crossing of the blood–brain barrier (BBB) via two main types of transcytosis mechanisms: adsorptive-mediated transcytosis (AMT) and receptor-mediated transcytosis (RMT). Their ability to accumulate in the brain can thus provide local sustained release of tumoricidal drugs at or near the site of GBM tumors. NP-based drug delivery has the potential to significantly reduce drug-related toxicity, increase specificity, and consequently improve the lifespan and quality of life of patients with GBM. Due to significant advances in the understanding of the molecular etiology and pathology of GBM, the efficacy of drugs loaded into vectors targeting this disease has increased in both preclinical and clinical settings. Multitargeting NPs, such as those incorporating multiple specific targeting ligands, are an innovative technology that can lead to decreased off-target effects while simultaneously having increased accumulation and action specifically at the tumor site. Targeting ligands can include antibodies, or fragments thereof, and peptides or small molecules, which can result in a more controlled drug delivery system compared to conventional drug treatments. This review focuses on GBM treatment strategies, summarizing current options and providing a detailed account of preclinical findings with prospective NP-based approaches aimed at improving tumor targeting and enhancing therapeutic outcomes for GBM patients.

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Funding

K.W. acknowledges support from the Government Pharmaceutical Organization (GPO) scholarship. J.C.Q. acknowledges support from the Alfred P. Sloan Foundation, the University of Iowa Graduate College, and the American Association for University Women. A.K.S acknowledges support from the Cancer Center support grant (P30 CA086862) and the Lyle and Sharon Bighley Chair in Pharmaceutical Sciences.

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  1. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA

    Kanawat Wiwatchaitawee, Juliana C. Quarterman, Sean M. Geary & Aliasger K. Salem

  2. Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, 52242, USA

    Aliasger K. Salem

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  1. Kanawat Wiwatchaitawee
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Wiwatchaitawee, K., Quarterman, J.C., Geary, S.M. et al. Enhancement of Therapies for Glioblastoma (GBM) Using Nanoparticle-based Delivery Systems. AAPS PharmSciTech 22, 71 (2021). https://doi.org/10.1208/s12249-021-01928-9

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