Induction of immunogenic cell death in murine colon cancer cells by ferrocene-containing redox phospholipid polymers.

Immunogenic cell death (ICD), activated by damage-associated molecular patterns (DAMPs), is an apoptotic cell death process that elicits antitumor immunity. Although anticancer drugs that can induce ICD are promising for cancer treatment, the design strategy for ICD inducers remains unclear. In this study, we demonstrated the cell-penetrating redox phospholipid polymer poly(2-methacryloyloxyethyl phosphorylcholine-co-vinyl ferrocene) (pMFc) inducing ICD in murine colon cancer CT26 cells. pMFc produced oxidative stress by extracting electrons from CT26 cells and induced the release of DAMPs, such as calreticulin, adenosine triphosphate, and high-mobility group box 1. Moreover, the injection of pMFc-treated CT26 cells inhibited tumor formation in subsequently challenged CT26 cells, indicating that pMFc elicited antitumor immunity through ICD. Using in vivo therapy, intratumoral injections of pMFc induced complete tumor regression in 20% (1/5) of mice. These results suggested that the redox phospholipid polymer provides a new option for ICD-inducing anticancer polymers.