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.

The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA. Previous studies have shown that Gal-DOX/siRNA-L inhibited tumor growth by combined effect of DOX and vimentin siRNA than single delivery of either DOX or vimentin siRNA. These Gal-DOX/siRNA-Ls showed stronger affinity to human hepatocellular carcinoma cells (Huh7) than other cells (lung epithelial carcinoma, A549). These liposomes also have demonstrated that novel hepatic drug/gene delivery systems composed of cationic lipid (DMKE: O,O’-dimyristyl-N-lysyl glutamate), cholesterol, galactosylated ceramide, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), and PEG₂₀₀₀-DSPE (distearoyl phosphatidyl ethanolamine) at 2:1:1:1:0.2 (moral ratios) can be used as an effective drug/gene carrier specifically targeting the liver in vivo. These results suggest that Gal-DOX-siRNA-L could effectively target tumor cells, enhance transfection efficacy and subsequently achieve the co-delivery of DOX and siRNA, demonstrating great potential for synergistic anti-tumor therapy.

Hee-Bin Park, Yun-Ji Kim, Seong-Min Lee, James S. Park and Keun-Sik Kim. BSL 2019;25:159-69. https://doi.org/10.15616/BSL.2019.25.2.159