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

Han Bi Ji; Cho Rim Kim; Chang Hee Min; Jae Hoon Han; Se-Na Kim; Cheol Lee; Young Bin Choy

doi:10.1002/btm2.10477

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

Bioeng Transl Med. 2023 Feb 1;8(3):e10477. doi: 10.1002/btm2.10477. eCollection 2023 May.

Authors

Han Bi Ji¹, Cho Rim Kim¹, Chang Hee Min¹, Jae Hoon Han¹, Se-Na Kim², Cheol Lee³, Young Bin Choy^{1

2

4}

Affiliations

¹ Interdisciplinary Program in Bioengineering College of Engineering, Seoul National University Seoul Republic of Korea.
² Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University Seoul Republic of Korea.
³ Department of Pathology Seoul National University College of Medicine Seoul Republic of Korea.
⁴ Department of Biomedical Engineering Seoul National University College of Medicine Seoul Republic of Korea.

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.

Keywords: cancer specific; chemodynamic therapy; drug delivery; hydrogen peroxide; metal–organic framework.