Abstract

Glioblastoma (GBM) is the most aggressive, infiltrative, and lethal brain tumor in humans. Despite the extensive advancement in the knowledge about tumor progression and treatment over the last few years, the prognosis of GBM is still very poor due to the difficulty of targeting drugs or anticancer molecules to GBM cells. The major challenge in improving GBM treatment implicates the development of a targeted drug delivery system, capable of crossing the blood–brain barrier (BBB) and specifically targeting GBM cells. Aptamers possess many characteristics that make them ideal novel therapeutic agents for the treatment of GBM. They are short single-stranded nucleic acids (RNA or ssDNA) able to bind to a molecular target with high affinity and specificity. Several GBM-targeting aptamers have been developed for imaging, tumor cell isolation from biopsies, and drug/anticancer molecule delivery to the tumor cells. Due to their properties (low immunogenicity, long stability, and toxicity), a large number of aptamers have been selected against GBM biomarkers and tested in GBM cell lines, while only a few of them have also been tested in in vivo models of GBM. Herein, we specifically focus on aptamers tested in GBM in vivo models that can be considered as new diagnostic and/or therapeutic tools for GBM patients’ treatment.

Highlights

  • GBM or astrocytoma grade IV is the most aggressive, infiltrative, and lethal brain tumor in humans [1]

  • Much attention has been focused on aptamers that are emerging as safe delivery vehicles for targeted cancer therapeutics

  • Some of the aptamers were isolated via selection against known specific GBM markers, whereas others were identified by selection against target cell surface molecules [11]

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Summary

Introduction

GBM or astrocytoma grade IV is the most aggressive, infiltrative, and lethal brain tumor in humans [1]. A library of oligonucleotides is incubated with the target cells and the unbound sequences are removed by washing, while the bound sequences are collected These sequences are able to bind specific molecules on the cell surface (positive selection). Some of the aptamers were isolated via selection against known specific GBM markers, whereas others were identified by selection against target cell surface molecules (cell-SELEX) [11]. These aptamers were used to deliver diagnostic or therapeutic agents for GBM diagnosis and treatment [6]. Only some of the GBM aptamers, able to reach the tumor site in vivo, are capable of efficiently treating this cancer [36,37,38,39,40,41,42,43,44,45,46]

Aptamers Showing In Vivo Therapeutic Effects
Aptamers Used as Antitumoral Molecules
AS1411 Aptamer
Aptamers Used as Drug Vehicles
GMT8 Aptamer
ATP Aptamer
Aptamers Able to Enhance GBM Therapy Efficacy
Aptamers Enhancing Radiotherapy Sensitivity
Immune-Modular Aptamers
Findings
Discussion
Conclusions
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