An intelligent self-supplying cascade system with monodispersing MOF-supported dual-nanozyme architectures for synergistic starvation and photothermal therapy.

Abstract

The applications of metal-organic frameworks (MOFs) are critically hindered by their inherent colloidal instability in physiological media, and challenges are further exacerbated by the hostile tumor microenvironment (TME) characterized by hypoxia and acidosis. To address these interrelated bottlenecks, our work engineers a core-shell nanoplatform by utilizing a UiO-66 MOF as the structural core and glucose oxidase (GOx) as the shell to realize stable monodispersity. GOx also allows further functionalization with dual-nanozymes, Au and manganese dioxide, which strategically provide robust in vivo stability and O2 self-supplying therapeutic modality. Manganese dioxide nanozyme catalyzes H2O2 to generate O2 specifically within the acidic TME, thereby alleviating tumor hypoxia and reversing the immunosuppressive acidic conditions. Au nanozyme with GOx promotes catalytic oxidation of glucose, generating a sustained flux of H2O2 that further fuels the manganese dioxide-mediated O2 production. This coupled enzymatic cascade establishes a positive feedback loop wherein starvation therapy is potentiated by the resulting increase in oxygen tension, culminating in amplified reactive oxygen species generation. Moreover, Au nanozyme serves dual functions: facilitating photothermal transduction to synergistically augment the cascade-induced oxidative stress and thereby achieving a robust starvation/photothermal synergy. This work not only presents a paradigm for constructing self-stabilizing, O2-generating MOF-based nanoplatforms that circumvent the limitations of the TME, but also offers a conceptually novel, chemo-free therapeutic strategy that leverages cascade nanozymatic reactions for highly efficacious and safe cancer treatment.

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