Photodynamic therapy (PDT) and radiotherapy (RT) are clinical treatment strategies for solid tumors. However, the uncontrolled proliferation of cancer cells leading to a hypoxic tumor microenvironment significantly reduces the efficacy. This study aimed to construct Au-PtNPs@Mn3O4 composite nanozymes for modulating tumor hypoxia and enhancing PDT and RT in cervical cancer. Au-PtNPs@Mn3O4 nanozymes were synthesized through self-assembly and electron transfer, followed by characterization and enzyme activity detection. Then, the cytotoxicity and distribution of Au-PtNPs@Mn3O4 nanozymes in vitro and in vivo were evaluated. After investigating the cellular uptake, the efficacy of Au-PtNPs@Mn3O4 nanozymes in vitro under normoxic and hypoxic atmospheres and in vivo was studied. Au-PtNPs@Mn3O4 nanozymes were designed with three different types of enzyme-like activities, including peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT). Also, Au-PtNPs@Mn3O4 has higher tumor-targeting efficiency without side effects. In vitro, Au-PtNPs@Mn3O4 synergistic therapy with PDT and RT significantly attenuated the cell proliferation of HeLa cells but facilitated ROS level (1O2 and •OH), cell apoptosis, and cell death under normoxic and hypoxic atmospheres. Also, Au-PtNPs@Mn3O4 synergistic therapy with PDT and RT could disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions. Moreover, Au-PtNPs@Mn3O4 synergistic therapy with PDT and RT also repressed the growth in tumor xenografts in vivo while promoting ROS generation. The Au-PtNPs@Mn3O4 nanozymes can improve the effect of PDT and RT by alleviating hypoxia in cervical cancer, thus achieving a multimodal synergistic therapy. This study presents a typical paradigm to harness hypoxic tumor microenvironments for highly effective cancer therapy.
Wang et al. (Wed,) studied this question.