Applications of Cancer Cell-Specific Aptamers in Targeted Delivery of Anticancer Therapeutic Agents

Abstract

Aptamers are single-stranded oligonucleotides that specifically bind and interact with their corresponding targets, including proteins and cells, through unique three-dimensional structures. Numerous aptamers have been developed to target cancer biomarkers with high specificity and affinity, and some are employed as versatile guiding ligands for cancer-specific drug delivery and anti-cancer therapeutics. In this review, we list the aptamers that target tumor surface biomarkers and summarize the representative applications of aptamers as agonists and antagonists that activate anti-cancer and inactivate pro-cancer biomarkers, respectively. In addition, we describe applications of aptamer-drug or aptamer-oligonucleotide conjugates that can deliver therapeutic agents, including small interfering RNAs, micro RNAs, short hairpin RNAs, and chemotherapeutic molecules, to cancer cells. Moreover, we provide examples of aptamer- conjugated nano-vehicles, in which cancer-targeting oligonucleotide aptamers are conjugated with nano-vehicles such as liposomes, micelles, polymeric nanoparticles, and quantum dots. Conjugation of aptamers with anti-cancer drugs and nano-vehicles will facilitate innovative applications of aptamer-based cancer therapeutics.

Peptide-Drug Conjugates and Their Targets in Advanced Cancer Therapies

“…The first component is the tumor-homing molecule. Multiple classes of molecules were investigated, including small molecules (Fitzgerald et al, 2016 ; Kue et al, 2016 ; Fernández et al, 2018 ), aptamers (Kaur et al, 2018 ; Kim et al, 2018 ), and polysaccharides (Choi et al, 2011 ). Even though these molecule classes led to promising results in preclinical studies, monoclonal antibodies (mAbs) evolved as fastest-growing drug class, with more than 30 mAbs being approved and more than 100 in clinical development over the past years (Carter and Lazar, 2018 ).…”

Aptamers, the Nucleic Acid Antibodies, in Cancer Therapy

“…Not only can aptamers be selected to target and inhibit cancer-specific molecules, but they can also be selected to recognize the surface structures of specific cell types and some of them can be endocytosed or taken in by the cells. The latter properties can be employed to deliver therapeutic agents such as cytotoxic drugs and therapeutic RNAs selectively into cancer cells to exert their activities while avoiding damaging normal cells [114][115][116][117]. Aptamers used for drug delivery mostly target cell membrane receptors that can internalize upon ligand binding, and successful deliveries of a variety of cargoes targeting different receptors have been reported to date [118] (see Figure 2).…”

DNA Aptamers for Functionalisation of DNA Origami Nanostructures

“…including a useful table of cell selectivity of aptamers [99]. Sgc8c, also used in the programmable DNA origami robot mentioned above, [63] targets protein tyrosine kinase 7 (PTK7), a transmembrane receptor highly expressed in cancer cell lines including T-cell acute lymphoblastic leukemia [69].…”