Data underlying the publication: Organochlorides Mediate Oxidation Reactions Induced by Low Dose Ionizing RadiationOrganochlorides Mediate Oxidation Reactions Induced by Low Dose Ionizing Radiation

The controlled release of drugs using local ionizing radiation presents a promising approach for targeted cancer treatment, particularly when applied in concurrent radio-chemotherapy. In these approaches, radiation-generated reactive species often play an important role. However, the reactive species that can be used to trigger release have low yield and lack selectivity. Here, we demonstrate the generation of highly oxidative species when aqueous solutions containing low concentrations of organochlorides (such as chloroform) are irradiated with ionizing radiation at therapeutically relevant doses. These reactive species were identified as peroxyl radicals, which formed in a reaction cascade between organochlorides and aqueous electrons. We employed stilbene-based probes to investigate the oxidation process, showing double bond oxidation and cleavage. To translate this reactivity into a radiation-sensitive material, we have synthesized a micelle forming amphiphilic block copolymer that has stilbene as the linker between two blocks. Upon exposure to ionizing radiation, the oxidation of stilbene led to the cleavage of the polymer, which induces the dissociation of the block-copolymer micelles and the release of loaded drugs.

利用局部电离辐射（ionizing radiation）实现药物控释，是一种颇具前景的靶向癌症治疗手段，尤其适用于同步放化疗（concurrent radio-chemotherapy）场景。此类疗法中，辐射诱导产生的活性物种往往发挥关键作用。然而，可用于触发药物释放的活性物种往往产率低下且缺乏选择性。本研究证实，当低浓度有机氯化物（organochlorides，如氯仿（chloroform））的水溶液在治疗相关剂量的电离辐射辐照下时，会生成强氧化性物种。经鉴定，此类活性物种为过氧自由基（peroxyl radicals），其通过有机氯化物与水合电子（aqueous electrons）间的级联反应生成。我们采用二苯乙烯（stilbene）类探针对氧化过程进行研究，观测到双键的氧化与断裂现象。为将该反应活性转化为辐射敏感材料，我们合成了一种可形成胶束（micelle）的两亲性嵌段共聚物（amphiphilic block copolymer），其以二苯乙烯作为两段链的连接基团。经电离辐射辐照后，二苯乙烯发生氧化，引发聚合物链断裂，进而诱导嵌段共聚物胶束解离并释放负载的药物。