Anticancer
therapies, which can induce cell death and elevate antitumor immune response in the meantime, are considered as effective treatments for many types of
cancers. Immunogenic cell death (ICD) induced by chemodrugs is a promising and typical strategy to achieve cell cytotoxicity and immunological enhancement together. However, due to the low level of ICD induction and less
tumor-targeting accumulation, application of traditional ICD inducers is limited. Here,
tumor-targeting core-shell magnetic nanoparticles (ETP-PtFeNP:α-
enolase targeting
peptide modified Pt-
prodrug loaded Fe3O4 nanoparticles) are developed to reinforce ICD induction of loaded-
oxaliplatin (IV)
prodrug. After
tumor-targeting accumulation and endocytosis,
platinum (IV) complexes are activated by intracellular reductive elimination to yield and release the Pt (II) congener,
oxaliplatin, leading to DNA lesions and
reactive oxygen species (ROS) generation. Simultaneously, in-progress-released ferric
ions elicit highly toxic ROS (·OH or ·OOH) burst and interfere with the intracytoplasmic redox balance (like endoplasmic reticulum stress), leading to ICD-associated immunogenicity enhancement and specific antitumor immune responses to kill the
tumor cells synergistically. Meanwhile, the transverse relaxation rate R 2 of ETP-PtFeNP is remarkably increased by more than three times while triggered by
reductant, suggesting ETP-PtFeNP a high-sensitivity T 2
contrast agent for magnetic resonance imaging.