Targeted delivery of Rab26 siRNA with precisely tailored DNA prism for lung cancer therapy.

Programmable DNA nanostructures are a new class of biocompatible, nontoxic nanomaterials. Nevertheless, their application in the field of biomedical research is still in its infancy, especially as drug delivery vehicles for gene therapy. In this study, a GTPase Rab26 was explored as a new potential therapeutic target using precisely tailored DNA prism for targeted lung cancer therapy. Specifically, a DNA prism platform with tunable targeting and siRNA loading capability is designed and synthesized. The DNA prisms were decorated with two functional units: a Rab26 siRNA as the drug and MUC-1 aptamers as targeting moiety for non-small cell lung cancer. The number and position of both siRNA and MUC-1 aptamer can be readily tuned. Native polyacrylamide gel electrophoresis (PAGE) and dynamic light scattering technique (DLS) demonstrate that all nanoprisms with different functionalities are self-assembled with high yield. It is also found that the cellular uptake of DNA prims is proportional to the aptamer number on each nanoprism, and the as-prepared DNA nanoprism show excellent anti-cancer activities and targeting capability. Current study suggest that by careful design, self-assembled DNA nanostructures are highly promising, customizable, multifuncitonal nanoplatform for potential biomedical applications, such as personalized precision therapy in the near future.