Aptamer-Modified Tetrahedral DNA Nanostructure for Tumor-Targeted Drug Delivery

Abstract

Tetrahedral DNA nanostructures (TDNs) are considered promising drug delivery carriers because they are able to permeate cellular membrane and are biocompatible and biodegradable. Furthermore, they can be modified by functional groups. To improve the drug-delivering ability of TDNs, we chose anticancer aptamer AS1411 to modify TDNs for tumor-targeted drug delivery. AS1411 can specifically bind to nucleolin, which is overexpressed on the cell membrane of tumor cells. Furthermore, AS1411 can inhibit NF-κB signaling and reduce the expression of bcl-2. In this study, we compared the intracellular localization of AS1411-modified TDNs (Apt-TDNs) with that of TDNs in different cells under hypoxic condition. Furthermore, we compared the effects of Apt-TDNs and TDNs on cell growth and cell cycle under hypoxic condition. A substantial amount of Apt-TDNs entered and accumulated in the nucleus of MCF-7 cells; however, the amount of Apt-TDNs that entered L929 cells was comparatively less. TDNs entered in much lower quantity in MCF-7 cells than Apt-TDNs. Moreover, there was little difference in the amount of TDNs that entered L929 cells and MCF-7 cells. Apt-TDNs can inhibit MCF-7 cell growth and promote L929 cell growth, while TDNs can promote both MCF-7 and L929 cell growth. Thus, the results indicate that Apt-TDNs are more effective tumor-targeted drug delivery vehicles than TDNs, with the ability to specifically inhibit tumor cell growth.

Effect of tetrahedral DNA nanostructures on proliferation and osteogenic differentiation of human periodontal ligament stem cells

“…27,43,44 This study explored the effects of TDNs on PDLSCs for the first time, and the results suggested that it could enhance proliferation and promote osteogenesis of PDLSCs. It could not only be used as a stimulator to adjust biological behaviours such as differentiation, anti-inflammatory response, proliferation and migration of cells, but could also be applied as a biosensor in molecular diagnosis and as a special carrier to transport ligands and drugs such as siRNA, AS1411 aptamers and DOX for molecular and targeted drug delivery.…”

Progress toward Understanding the Interactions between DNA Nanostructures and the Cell

“…Attaching ligands to tile‐based DNA nanostructures for targeting cell‐surface receptors is an emerging trend for improving cellular uptake and targeting selectivity. In 2017, Li et al decorated TDNs with AS1411, an anticancer aptamer that targets the tumor marker nucleolin, and evaluated their uptake by MCF‐7 breast cancer cells and noncancerous L929 fibroblasts . For MCF‐7 cells, the authors showed that such aptamer‐modified TDNs enter the cells four times more abundantly than TDNs without aptamers.…”

Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

“…They have high thermal and chemical stability due to the strong phosphodiester bonds present in their nucleic acid backbone . They have been investigated for use as standalone biological drugs or pharmaceutical delivery vehicles for targeted drug delivery applications …”

“…[129] They have been investigated for use as standalone biological drugs or pharmaceutical delivery vehicles for targeted drug delivery applications. [130][131][132] Pegatanib is the first aptamer drug approved by FDA to treat the ocular disease called age-related vascular macular degeneration mostly in the elderly. Pegatanib works by antagonizing the vascular endothelial growth factor (VEGF) to block the receptor binding of VEGF, leading to minimized vascular permeability and angiogenesis.…”