Gamma-glutamyl transferase(GGT) is an attractive receptor for targeted cancer therapy, but its low density on tumor surfaces often limits therapeutic efficacy. Since reactive oxygen species(ROS) induce apoptosis and upregulate GGT, we hypothesized that GGT-targeting prooxidants could drive a self-boosting therapeutic cycle. Leveraging this rationale, we developed GLOXmp, a glutamic acid-functionalized nanoamplifier engineered to generate ROS and deplete glutathione. GLOXmp disrupts intracellular redox balance, eliciting potent cytotoxicity while reprogramming tumor cells to overexpress GGT. This upregulation potentiates the receptor-mediated uptake of subsequent doses, establishing a self-perpetuating positive feedback loop. In xenograft models, this strategy significantly amplified tumor accumulation and achieved complete eradication without systemic toxicity. These findings demonstrate a novel approach to overcoming tumor heterogeneity via oxidative stress-mediated reprogramming.