Intravenously injected high-dose vitamin C (VC) induces extracellular HO, which can penetrate into the tumor cells and suppress tumor growth. However, extracellular labile iron ions in the tumor decompose HO via the Fenton reaction, limiting the therapeutic effect. In this regard, we recently developed a polymeric iron chelator that can inactivate the intratumoral labile iron ions. Here, we examined the effect of our polymeric iron chelator on the high-dose VC therapy in and . In the study, the polymeric iron chelator could inactivate the extracellular labile iron ions and prevent the unfavorable decomposition of VC-induced HO, augmenting pro-oxidative damage to DNA and inducing apoptosis in cultured cancer cells. Even in the study, the polymeric iron chelator significantly improved the antitumor effect of VC in subcutaneous DLD-1 and CT26 tumors in mice, while conventional iron chelators could not. This work indicates the importance of modulating tumor-associated iron ions in the high-dose VC therapy and should contribute to a better understanding of its mechanism.
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