Redirecting Tumor Evolution with Nanocompiler Precision for Enhanced Therapeutic Outcomes

Abstract Precisely programming the highly plastic tumor expression profile to render it devoid of drug resistance and metastatic potential presents immense challenges. Here, a transformative nanocompiler designed to reprogram and stabilize the mutable state of tumor cells is introduced. This nanocompiler features a trio of components: 2‐deoxy‐ d ‐glucose‐modified lipid nanoparticles to inhibit glucose uptake, iron oxide nanoparticles to induce oxidative stress, and a deubiquitinase inhibitor to block adaptive protein profile changes in tumor cells. By specifically targeting the hypermetabolic nature of tumors, this approach disrupted their energy production, ultimately fostering a state of vulnerability and impeding their ability to adapt and resist. The results of this study indicate a substantial reduction in tumor growth and metastasis, thus demonstrating the potential of this strategy to manipulate tumor protein expression and fate. This proactive nanocompiler approach promises to steer cancer therapy toward more effective and lasting outcomes.