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

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.