Dual-Modal Therapeutic Role of the Lactate Oxidase-Embedded Hierarchical Porous Zeolitic Imidazolate Framework as a Nanocatalyst for Effective Tumor Suppression.

The increasing evidence supports the fact that lactate in the tumor microenvironment (TME) plays a vital role in tumor proliferation, metastasis, and recurrence, which in turn is emerging as one of the most interesting molecular targets for tumor treatment. Here, hierarchical porous zeolitic imidazolate framework-8 (ZIF-8) as the nanocarrier is fabricated to simultaneously load lactate oxidase (LOD) and Fe3O4 nanoparticles (NPs), called LOD & Fe3O4@ZIF-8 NPs (LFZ NPs), for tumor therapy. On one hand, the sharp consumption of lactate in the TME by LOD will change the essential "soil" where tumor cells live so as to suppress tumor rapid growth. On the other hand, hydrogen peroxide (H2O2) is produced in the TME from the oxidation of lactate catalyzed by LOD and subsequently converted to highly toxic hydroxyl radicals (•OH) catalyzed by Fe3O4 NPs via Fenton-like reactions to kill tumor cells. Based on the endogenous catalysis, this dual-modal strategy of tumor therapy based on lactate is simple, safe, and effective, which deserves to be well concerned.