Nanozyme hydrogel for enhanced alkyl radical generation and potent antitumor therapy†
Abstract
Alkyl radicals (R˙), which do not rely on oxygen generation for causing cellular stress, have been applied in tumor treatment, but a large amount of glutathione (GSH) in the tumor cells reacts with alkyl radicals, thereby reducing their antitumor effect. In this study, an enhanced alkyl radical generation system responsive to near-infrared light was designed. The alkyl radical trigger 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) and nanozyme pyrite (FeS2) were encapsulated in agarose hydrogel to prepare the AIPH–FeS2–hydrogel (AFH) system. FeS2 can be used as a photothermal agent to convert near-infrared light energy into heat energy, leading to the dissolution of the hydrogel. AIPH is simultaneously induced to produce alkyl radicals. FeS2 can also be used as an oxidative stress amplifier to reduce intracellular GSH content, thereby boosting the therapeutic effect of alkyl radicals. Eventually, the oxygen-independent free radicals generated by the AFH system under near-infrared laser irradiation and photothermal treatment can kill cancer cells through the synergistic oxidation/photothermal effect. The AFH system developed herein provides new insights into enhancing the therapeutic effect of alkyl radicals.