Irradiation of aqueous solutions containing alkyl chlorides generates peroxyl radicals by reactions of alkyl chlorides, aqueous electrons, and dissolved oxygen. The peroxyl radical can oxidize thioethers to sulfoxides, a transformation that has relevance for targeted or triggered drug delivery. However, small-molecule alkyl chlorides can induce liver damage, which limits their potential for application in anticancer therapy. Here, we show that alkyl chlorides bound to a hydrophilic random copolymer chain behave similar to small-molecule alkyl chlorides. Our work shows that using polymeric alkyl chlorides can be an alternative to small-molecule alkyl chlorides provided that the alkyl chloride functionalities are easily accessible to aqueous electrons.

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 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.