Site-specific anchoring aptamer C2NP on DNA origami nanostructures for cancer treatment

Abstract

Because of the remarkable features, including biocompatibility and biodegradability, DNA origami nanostructures have drawn much attention as ideal carriers for drug delivery. However, the cellular uptake of DNA origami nanostructures was a passive targeting process, resulting in limited therapeutic effect. To address this problem, we anchored the aptamer C2NP (Apt) on rectangular DNA origami nanostructures (RE) to enhance the tumor targeting properties and anticancer effects of doxorubicin (DOX). Apt was anchored onto RE with low or high density (RE-4Apt, RE-16Apt), followed by incubation with DOX to obtain DOX@RE-4Apt and DOX@RE-16Apt. The results showed that DOX@RE-4Apt and DOX@RE-16Apt exhibited excellent biocompatibility and targeting ability, as well as a synergic biological effect with chemotherapy on cancer therapy. More importantly, after conjugation with RE, the bioactivity of Apt was significantly increased. These results revealed that Apt anchored DNA nanostructures not only are potential carriers for precise therapy, but also supply a strategy to enhance the bioactivity of aptamers.