Pt(II) drugs are a widely used chemotherapeutic, yet their side effects can be severe. Here we show that the radiation-induced reduction of Pt(IV) complexes to cytotoxic Pt(II) drugs is rapid, efficient and applicable in water, that it is mediated by hydrated electrons from water radiolysis and that the X-ray-induced release of Pt(II) drugs from an oxaliplatin prodrug in tumours inhibits their growth, as we show with nearly complete tumour regression in mice with subcutaneous human tumour xenografts. The combination of low-dose radiotherapy with a Pt(IV)-based antibody–trastuzumab conjugate led to the tumour-selective release of the chemotherapeutic in mice and to substantial therapeutic benefits. The radiation-induced local reduction of platinum prodrugs in the reductive tumour microenvironment may expand the utility of radiotherapy.

Pt(II) 药物是一种广泛使用的化疗药物，但其副​​作用可能很严重。在这里，我们表明，辐射诱导的 Pt(IV) 配合物还原成细胞毒性 Pt(II) 药物是快速、有效的，并且适用于水中，它是由水辐射解产生的水合电子介导的，并且 X 射线诱导的释放奥沙利铂前药中的 Pt(II) 药物在肿瘤中抑制肿瘤生长，正如我们在皮下人类肿瘤异种移植小鼠中肿瘤几乎完全消退所显示的那样。低剂量放疗与基于 Pt(IV) 的抗体-曲妥珠单抗结合物的组合导致化疗药物在小鼠体内选择性释放，并产生了显着的治疗效果。放射诱导的铂前药在减少的肿瘤微环境中的局部减少可能会扩大放射治疗的效用。