Synergistic anticancer effects of plasma-activated hydrogel and CuMOF by inducing hybrid oxidative stress

Although cold atmospheric plasma-activated hydrogel (PAH) loaded with plasma-generated reactive oxygen and nitrogen species (RONS) exhibits significant anticancer potential arising from slow RONS release, challenges, such as low RONS delivery efficiency, remain. The copper metal-organic framework (CuMOF), a new class of nanomaterials, induces the accumulation of reactive oxygen species (ROS), leading to apoptosis. Herein, a plasma-activated Pluronic F127 hydrogel (PAHPF127) is prepared by air discharge plasma to synergize with CuMOF for enhanced anticancer effects. The PAHPF127can load, store, and slow-release various RONS species generated by plasma. The plasma treatment does not adversely affect the temperature sensitivity, injectability, absorbance, or rheological properties of the Pluronic F127 hydrogel. In vitro studies reveal that PAHPF127induces oxidative stress, leading to B16F10 melanoma cell death by lowering cell viability and increasing intracellular ROS levels. In contrast, the introduction of oxidative stress mediated by PAHPF127in cancer cells is significantly greater when the hydrogel is used in combination with CuMOF compared to when it is used alone. In vivo results demonstrate that the synergy of PAHPF127 and Cu-MOF elicits a pronounced synergistic anticancer efficacy. The PAHPF127-CuMOF markedly attenuates neoplastic proliferation while concomitantly inducing higher cell apoptosis and excellent biosafety. The findings suggest that combining PAH with novel nanomaterials is a promising approach to enhance the anticancer efficacy and offers a new strategy for cancer therapy.