Gene-targeted therapies are revolutionizing cancer treatment due to their high specificity and low toxicity. Among these, ribozymes hold promise as independent gene therapy agents capable of directly cleaving target mRNAs. The pistol ribozyme, discovered in 2015, stands out for its compact structure and robust cleavage activity, making it a promising candidate for RNA silencing under physiological conditions. However, its clinical application is limited by nuclease susceptibility and biological barrier penetration. To overcome these obstacles, this study presents an innovative gene-regulation strategy incorporating engineered pistol ribozymes into a spherical nucleic acid (SNA) nanocarrier. This catalytic SNA nanocarrier, built on a DNA core-shell framework, combines the ribozyme with doxorubicin (Dox) to form the