RA16-Modified DNA Tetrahedra: Targeted Delivery and Inhibition in Non-Small Cell Lung Cancer

Lung cancer remains the leading cause of cancer-related deaths, with the five-year survival rate for non-small cell lung cancer (NSCLC) patients as low as 10%. RNA aptamer RA16 has shown potential as a targeted therapy, binding specifically to NSCLC NCI-H460 cells and inhibiting proliferation in murine models. However, its clinical application is limited by poor in vivo stability. To overcome this, we developed RA16-functionalized DNA nanomaterials, combining the aptamer's targeting ability with the stability and high drug-loading capacity of tetrahedral DNA (TD) nanostructures. In vitro assays confirmed the biocompatibility, stability, and high drug-loading capacity of RA16-TD nanoparticles. RA16-TD enhanced cell binding and internalization by 10-fold compared to free RA16. In H460 xenograft mouse models, RA16-TD accumulation at the tumor site was 2.43-fold higher than free RA16 at 72 h postadministration. Furthermore, RA16-TD-loaded Epirubicin showed superior therapeutic efficacy, with a tumor inhibition rate of 77.8%, compared to 44.6% for free Epirubicin and 51.7% for RA16-Epirubicin. These results highlight the potential of RA16-functionalized DNA nanomaterials as a promising platform for targeted therapy in NSCLC, offering avenues for clinical application.