한빛사 논문
Han Bi Ji1, Cho Rim Kim1, Chang Hee Min1, Jae Hoon Han1, Se-Na Kim2, Cheol Lee3, Young Bin Choy1,2,4
1Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul, Republic of Korea
2Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul, Republic of Korea
3Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
4Department of Biomedical Engineering, Seoul National University College of Medicine,Seoul, Republic of Korea
Correspondence: Young Bin Choy
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.
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