Aptamer-Based In Vivo Therapeutic Targeting of Glioblastoma

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.

Synthesis of Poly(Malic Acid) Derivatives End-Functionalized with Peptides and Preparation of Biocompatible Nanoparticles to Target Hepatoma Cells

“…At the beginning of the 20th century, Paul Ehrlich coined the term “Magic Bullet”, postulating that the targeting of drug towards specific diseased cells/tissues could be achieved without affecting healthy ones [ 1 ]. Ever since, tremendous research work has been done for designing efficient site-specific drugs using various ligand molecules, such as monoclonal antibodies (mAbs) [ 2 , 3 , 4 ], vitamins [ 2 , 5 , 6 , 7 ], carbohydrates [ 2 , 8 ], and aptamers [ 9 , 10 , 11 ]. More recently, short synthetic peptides have gained interest as targeting agents in the design of site-specific nanomedicines for therapy and/or diagnosis of several pathologies, especially cancers [ 2 , 12 , 13 , 14 , 15 , 16 ].…”

Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy

“…They are obtained by an automated chemical synthesis with minimal lot-to-lot variations and can be chemically modified to improve their biological stability [ 12 ]. A variety of aptamers and aptamer-based constructs have been reported, which can bind and internalize into the tumor cells, particularly glioma cells, in vitro and in vivo (see the reviews [ 13 , 14 ]). Moreover, different chemical approaches allow for multiple boron loading of synthetic nucleic acids [ 15 ].…”

Pheno-SELEX: Engineering Anti-Metastatic Aptamers through Targeting the Invasive Phenotype Using Systemic Evolution of Ligands by Exponential Enrichment

“…Aptamers could be designed to specifically target metastatic cells for delivery of radionucleotides [ 34 ]. In addition to the already approved use of aptamers for macular degeneration [ 4 ], advances in the clinical use of aptamers suggest that they will become viable therapeutic tools in the next few years [ 35 , 36 , 37 ]. Thus, the identification of aptamers that functionally inhibit cancer phenotypes can be poised for clinical use.…”