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Mitochondria are a major source of reactive oxygen species (ROS), and many cancer cells exhibit elevated basal ROS levels, making mitochondrial redox modulation an attractive strategy for redox\u2010based cancer therapy. However, efficient mitochondrial delivery of redox\u2010active agents remains challenging. Small\u2010molecule redox agents often require hydrophobicity that compromises their water solubility and increases their non\u2010specific toxicity. Although synthetic polymers improve solubility and biocompatibility, they are predominantly taken up via endocytosis, which often requires additional elements for endosomal escape to achieve efficient cytosolic access and mitochondrial delivery. In this study, we developed mitochondria\u2010directed phospholipid polymers based on 2\u2010methacryloyloxyethyl phosphorylcholine (MPC) and redox\u2010active ferrocene using a simple copolymerization strategy. We leveraged the cell\u2010penetrating characteristics of amphiphilic MPC copolymers bearing hydrophobic ferrocene units to access the cytosol and introduced a mitochondria\u2010directed motif by copolymerizing a triphenylphosphonium (TPP)\u2010containing monomer. The TPP\u2010bearing polymer exhibited higher in\u00a0vitro anticancer activity than the non\u2010directed polymer in CT26 mouse colon cancer cells. Confocal co\u2010localization analysis revealed that the non\u2010directed polymer was widely distributed throughout the cells, whereas the TPP\u2010bearing polymer showed significantly higher mitochondrial co\u2010localization. The TPP\u2010bearing polymer also induced higher intracellular ROS levels than the non\u2010directed polymer. Moreover, intratumoral administration of the TPP\u2010bearing polymer significantly suppressed CT26 tumor growth in mice. Overall, this study provides a simple design strategy for organelle\u2010directed redox\u2010active polymers toward redox\u2010based cancer therapy.<\/jats:p>","DOI":"10.1111\/cas.70547","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:21:26Z","timestamp":1790382086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondria\u2010Directed Redox Phospholipid Polymers for Cancer Therapy"],"prefix":"10.1111","author":[{"given":"Yuma","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Chemical Systems Engineering, Graduate School of Engineering Nagoya University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Chemical Systems Engineering, Graduate School of Engineering Nagoya University  Nagoya 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