Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics

TLDR

Nanotechnology enables diverse nanostructures for biomedicine, yet a simple, target‑specific, economical, biocompatible drug delivery platform achieving high maximum tolerated doses remains needed. The study introduces aptamer‑tethered DNA nanotrains as carriers for targeted drug transport in cancer therapy. The aptNTrs self‑assemble from two short DNA strands initiated by modified aptamers that act as locomotives guiding the trains to cancer cells, while tandem boxcars carry high drug payloads to induce selective cytotoxicity. In a mouse xenograft model, aptNTrs increased maximum tolerated dose in non‑target cells, achieved potent antitumor efficacy with reduced side effects, and enabled intracellular signaling via fluorophore dequenching, demonstrating their promise as a targeted drug transport platform for cancer theranostics.

Abstract

Nanotechnology has allowed the construction of various nanostructures for applications, including biomedicine. However, a simple target-specific, economical, and biocompatible drug delivery platform with high maximum tolerated doses is still in demand. Here, we report aptamer-tethered DNA nanotrains (aptNTrs) as carriers for targeted drug transport in cancer therapy. Long aptNTrs were self-assembled from only two short DNA upon initiation by modified aptamers, which worked like locomotives guiding nanotrains toward target cancer cells. Meanwhile, tandem “boxcars” served as carriers with high payload capacity of drugs that were transported to target cells and induced selective cytotoxicity. aptNTrs enhanced maximum tolerated dose in nontarget cells. Potent antitumor efficacy and reduced side effects of drugs delivered by biocompatible aptNTrs were demonstrated in a mouse xenograft tumor model. Moreover, fluorophores on nanotrains and drug fluorescence dequenching upon release allowed intracellular signaling of nanotrains and drugs. These results make aptNTrs a promising targeted drug transport platform for cancer theranostics.