Targeted Oxidative Burst Therapy: Dye-Conjugated RNA for Tumor-Specific Hydrogen Peroxide Overproduction and Self-Lysis

Cancer remains a leading cause of mortality worldwide, with conventional therapiessuch as chemotherapy and radiation often limited by systemic toxicity and resistance.This paper proposes a novel targeted oxidative burst therapy (TOBT) that utilizespositron emission tomography (PET) contrast dyes conjugated to RNA payloads en-coding a spike-protein membrane-inserting domain. The conjugate combines a PETdye for tumor targeting with RNA encoding a spike-protein membrane-inserting do-main, triggering mechanical lysis upon local H2O2 overproduction. Activation occursthrough near-infrared light, pH-sensitive mechanisms, or hypoxia-responsive promotersto ensure precise delivery and activation within the tumor microenvironment. The ap-proach is designed to achieve minimal off-target effects due to rapid renal clearance ofthe conjugate and tumor-specific activation of H2O2 overproduction. Preclinical viabil-ity appears high, with existing technologies supporting rapid advancement to in vitroand animal model studies. This therapy offers superior targeting and the potential forsingle-dose efficacy compared with systemic treatments.