SiRNA-Templated 3D Framework Nucleic-Acids for Chemotactic Recognition, and Programmable and Visualized Precise Delivery for Synergistic Cancer Therapy

Developments in framework nucleic acids (FNAs) are limited by complicated synthesis, by-product interference, and low framework utilization. Herein, simple core–shell spherical 3D FNAs (ST-SFNAs) preparation is presented based on siRNA-templated linear polymerization followed by hybridization chain reaction branched polymerization. Without by-products, all components exhibited their special functions to obtain high space utilization of ST-SFNAs. ST-SFNAs were covered by catalase and folic acid-functionalized liposome membranes. The catalase endowed ST-SFNAs with chemotactic activities in the H2O2 reaction catalyzed by catalase. Furthermore, combined with functionalized folic acids' targeting folate receptors, the synergistic chemotactic recognition of cancer cells was obtained. This dramatically promoted targeted cellular uptakes compared with traditional active or passive targeting pathways. Subsequently, the cascaded-logical programmable release of drugs was precisely controlled by targeting glutathione and ATP (via S–S bond and ATP aptamer on the inner g-DNA cover). This was visualized by “turn on” fluorescent signals generated by special hybridization of released hairpin DNAs with survivin mRNA biomarkers. Simultaneously, biocompatible synergistic therapy was achieved by simultaneously releasing doxorubicin and siRNA. With its high utilization for synergistic chemotactic recognition, programmable and visualized delivery, as well as synergistic therapy, an efficient platform for maximizing the therapeutic efficacy has been developed. This would initiate further FNA-based material development for a variety of biological applications.