The efficacy of radiotherapy is often significantly compromised due to tumor hypoxia.We developed a novel strategy to overcome tumor hypoxia and enhance radiotherapy using a low-toxicity catalyst with high-Z atoms.We ...The efficacy of radiotherapy is often significantly compromised due to tumor hypoxia.We developed a novel strategy to overcome tumor hypoxia and enhance radiotherapy using a low-toxicity catalyst with high-Z atoms.We employed in situ electrocatalytic oxygen generation in the tumor to improve the hypoxic state and sensitize radiotherapy.By employing multi-dentate chelating ligands in conjunction with a high-Z Ru metal center,we constructed a low-toxicity electrocatalyst for water oxidation:Ru(bbp)(Py)_(2)Cl.On the one hand,Ru(bbp)(Py)_(2)Cl served as a low-toxicity catalyst for electrocatalytic oxygen production,improving the hypoxic condition in the tumor.On the other hand,Ru enhanced the sensitivity of radiotherapy in response to X-ray,significantly boosting the therapeutic effect.In vitro and vivo experimental results revealed that our in situ electrocatalytic oxygen-production strategy could directly generate oxygen within the body,effectively alleviating tumor hypoxia.Furthermore,this strategy employed a multi-faceted sensitization mechanism by producing excess reactive oxygen species,which disrupted mitochondrial function and induced activation of the apoptosis-regulating proteins caspase-3 and caspase-9,ultimately triggering apoptosis and achieving significant anti-cancer effects.This research provides a novel approach to improving the hypoxic environment in tumors,but also opens new avenues for sensitizing radiotherapy,potentially leading to breakthrough advancements in cancer treatment.展开更多
基金supported by the National Science Fund for Distinguished Young Scholars(82225025)the National Natural Science Foundation of China(22177038,21877049,32171296,82372103)+1 种基金China National Postdoctoral Program for Innovative Talent(BX20240141)K.C.Wong Education Foundation.
文摘The efficacy of radiotherapy is often significantly compromised due to tumor hypoxia.We developed a novel strategy to overcome tumor hypoxia and enhance radiotherapy using a low-toxicity catalyst with high-Z atoms.We employed in situ electrocatalytic oxygen generation in the tumor to improve the hypoxic state and sensitize radiotherapy.By employing multi-dentate chelating ligands in conjunction with a high-Z Ru metal center,we constructed a low-toxicity electrocatalyst for water oxidation:Ru(bbp)(Py)_(2)Cl.On the one hand,Ru(bbp)(Py)_(2)Cl served as a low-toxicity catalyst for electrocatalytic oxygen production,improving the hypoxic condition in the tumor.On the other hand,Ru enhanced the sensitivity of radiotherapy in response to X-ray,significantly boosting the therapeutic effect.In vitro and vivo experimental results revealed that our in situ electrocatalytic oxygen-production strategy could directly generate oxygen within the body,effectively alleviating tumor hypoxia.Furthermore,this strategy employed a multi-faceted sensitization mechanism by producing excess reactive oxygen species,which disrupted mitochondrial function and induced activation of the apoptosis-regulating proteins caspase-3 and caspase-9,ultimately triggering apoptosis and achieving significant anti-cancer effects.This research provides a novel approach to improving the hypoxic environment in tumors,but also opens new avenues for sensitizing radiotherapy,potentially leading to breakthrough advancements in cancer treatment.
