Abstract
Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood–brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood–brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.
Highlights
Glioblastoma or glioblastoma multiforme (GBM) is a highly malignant form of glioma, which is the tumor associated with neoplastic glial cells in the brain, including oligodendrocytes, astrocytes, and ependymal cells [1]
In line with their previous observations, histological and immunohistochemical analysis of the animal samples treated with DOX–poly(isohexyl cyanoacrylate) (PIHCA) nanoparticles revealed a decrease in tumor size, proliferation index, tumor vessel density, and necrotic areas when compared to the groups treated with empty PIHCA nanoparticles or DOX in solution
It was demonstrated that coincubation of glioma cells (U188, SF767, and GBM6) for 72 h with CTX-conjugated CS nanoparticles loaded with TMZ achieved 2–6-fold higher uptake and 50–90% reduction of IC50 values for the drug when compared to coincubation of CS nanoparticles without CTX and free TMZ
Summary
Glioblastoma or glioblastoma multiforme (GBM) is a highly malignant form of glioma, which is the tumor associated with neoplastic glial cells in the brain, including oligodendrocytes, astrocytes, and ependymal cells [1]. The etiology of GBM remains unknown, one of the identified risk factors is the abnormal exposure to ionizing radiation [4] This disease has a complex genetic expression, including gains of chromosomes 7 and 19, losses of chromosomes 10 and 13, amplification of epidermal growth factor receptor (EGFR) and MDM2, mutation of PTEN, NF1, PDGFRA1, IDH1/2, and deletion of CDKN2A/B [1]. (4) the blood–brain tumor barrier prevents most chemotherapies or other anticancer treatments to reach the brain tumor tissue, resulting in a poor cytotoxic activity and the development of drug resistance [6] For all these reasons, the survival period for most of the patients with GBM is only approximately. 1 year, and only 5% of patients survive longer than 5 years [7]
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