Tumor-specific activated polymeric nanotuners disrupt positive feedback cycle of hypoxia and apoptosis evasion for potent cancer radiotherapy

) for hypoxia alleviation, thus upregulating the expression of proapoptotic protein Smac. Furthermore, the apoptotic-inducing peptide modified on the core surface further boosts the Smac-induced apoptosis signal, intervening in tumor apoptosis evasion and ultimately realizing the efficient radiotherapeutic efficiency by blocking this vicious cycle. In vivo studies demonstrated that treatment with polymeric nanotuners remarkably enhances radiation-mediated tumor ablation without perceptible side effects. This study sheds light on the innovative attempt to specifically interfere with the feedback cycle in tumor radioresistance, pioneering the way for achieving safe and efficient cancer therapies.