Fe-containing metal-organic framework with D-penicillamine for cancer-specific hydrogen peroxide generation and enhanced chemodynamic therapy.

ABSTRACT: Chemodynamic therapy (CDT) is based on the production of cytotoxic reactive oxygen species, such as hydroxyl radicals (^•OH). Thus, CDT can be advantageous when it is cancer-specific, in terms of efficacy and safety. Therefore, we propose NH₂-MIL-101(Fe), a Fe-containing metal-organic framework (MOF), as a carrier of Cu (copper)-chelating agent, d-penicillamine (d-pen; i.e., the NH₂-MIL-101(Fe)/d-pen), as well as a catalyst with Fe-metal clusters for Fenton reaction. NH₂-MIL-101(Fe)/d-pen in the form of nanoparticles was efficiently taken into cancer cells and released d-pen in a sustained manner. The released d-pen chelated Cu that is highly expressed in cancer environments and this produces extra H₂O₂, which is then decomposed by Fe in NH₂-MIL-101(Fe) to generate ^•OH. Therefore, the cytotoxicity of NH₂-MIL-101(Fe)/d-pen was observed in cancer cells, not in normal cells. We also suggest a formulation of NH₂-MIL-101(Fe)/d-pen combined with NH₂-MIL-101(Fe) loaded with the chemotherapeutic drug, irinotecan (CPT-11; NH₂-MIL-101(Fe)/CPT-11). When intratumorally injected into tumor-bearing mice in vivo, this combined formulation exhibited the most prominent anticancer effects among all tested formulations, owing to the synergistic effect of CDT and chemotherapy.

SUBMITTER: Ji HB 

PROVIDER: S-EPMC10189484 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature