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A receptor-mediated landscape of druggable and targeted nanomaterials for gliomas
Leonardo Delello Di Filippo1, Suzana Gonçalves de Carvalho1, Jonatas Lobato Duarte1
1School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.
Abstract:
Gliomas are the most common type of brain cancer, and among them, glioblastoma multiforme (GBM) is the most prevalent (about 60% of cases) and the most aggressive type of primary brain tumor. The treatment of GBM is a major challenge due to the pathophysiological characteristics of the disease, such as the presence of the blood-brain barrier (BBB), which prevents and regulates the passage of substances from the bloodstream to the brain parenchyma, making many of the chemotherapeutics currently available not able to reach the brain in therapeutic concentrations, accumulating in non-target organs, and causing considerable adverse effects for the patient. In this scenario, nanocarriers emerge as tools capable of improving the brain bioavailability of chemotherapeutics, in addition to improving their biodistribution and enhancing their uptake in GBM cells. This is possible due to its nanometric size and surface modification strategies, which can actively target nanocarriers to elements overexpressed by GBM cells (such as transmembrane receptors) related to aggressive development, drug resistance, and poor prognosis. In this review, an overview of the most frequently overexpressed receptors in GBM cells and possible approaches to chemotherapeutic delivery and active targeting using nanocarriers will be presented.
Insights
Nanocarriers offer a promising solution for glioblastoma multiforme (GBM) treatment by overcoming the blood-brain barrier (BBB). These nanocarriers improve drug delivery and targeting to GBM cells, enhancing therapeutic efficacy.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Gliomas are the most common brain cancers, with glioblastoma multiforme (GBM) being the most aggressive subtype.
- The blood-brain barrier (BBB) significantly hinders effective chemotherapy delivery to brain tumors, leading to systemic toxicity.
- Current GBM treatments face challenges due to poor drug bioavailability and off-target accumulation.
Purpose of the Study:
- To review nanocarrier strategies for improving chemotherapeutic delivery in GBM.
- To identify overexpressed receptors in GBM cells for targeted nanocarrier delivery.
- To explore enhanced drug bioavailability and GBM cell uptake using nanocarriers.
Main Methods:
- Review of current literature on nanocarrier applications in GBM treatment.
- Analysis of GBM cell pathophysiology and blood-brain barrier challenges.
- Identification of GBM-specific overexpressed cell surface receptors.
Main Results:
- Nanocarriers can enhance the brain bioavailability of chemotherapeutics.
- Surface modification of nanocarriers enables active targeting of GBM cells.
- Targeting overexpressed receptors can improve drug uptake and therapeutic outcomes.
Conclusions:
- Nanocarriers represent a viable strategy to overcome BBB limitations in GBM treatment.
- Targeted nanocarrier delivery holds potential for improved GBM therapy with reduced side effects.
- Further research into nanocarrier design and GBM receptor targeting is warranted.
