Targeted Delivery of Rab26 siRNA with Precisely Tailored DNA Prism for Lung Cancer Therapy

Abstract 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 investigated as a new potential therapeutic target using a precisely tailored DNA nanoprism for targeted lung cancer therapy. Specifically, a DNA nanoprism platform with tunable targeting and siRNA loading capability is designed and synthesized. The as‐prepared DNA prisms were decorated with two functional units: a Rab26 siRNA as the drug and MUC‐1 aptamers as a targeting moiety for non‐small cell lung cancer. The number and position of both siRNA and MUC‐1 aptamers can be readily tuned by switching two short, single‐stranded DNA. 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 prisms is proportional to the aptamer number on each nanoprism, and the as‐prepared DNA nanoprism show excellent anti‐cancer activities and targeting capability. This study suggests that by careful design, self‐assembled DNA nanostructures are highly promising, customizable, multifunctional nanoplatforms for potential biomedical applications, such as personalized precision therapy.