Tumor Microenvironment‐Triggered Aggregated Magnetic Nanoparticles for Reinforced Image‐Guided Immunogenic Chemotherapy

Abstract

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 Fe 3 O 4 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.

Recent Progress in Ferroptosis Inducers for Cancer Therapy

“…Most previous studies used solid iron‐based nanocrystals, such as iron oxide nanoparticles and FePt nanoparticles as the iron source to trigger Fenton chemistry in tumor . The amount of Fe 2+ /Fe 3+ ions released from these nanoparticles is influenced by pH value and reductive environment . Nevertheless, these solid nanocrystals show limited iron releasing efficiency.…”

MnOx Nanospikes as Nanoadjuvants and Immunogenic Cell Death Drugs with Enhanced Antitumor Immunity and Antimetastatic Effect

“…It has been reported that CDT and ferroptosis can elicit ICD by triggering dying tumor cells to generate damage-associated molecular patterns (DAMPs). [16] To study whether MnO x can elicit ICD, the crucial ICD biomarkers were detected. [17] Significant cell-surface calreticulin (CRT) exposure was observed in MnO x -treated group (Figure 2 a; Figure S28).…”

Engineering nanomedicines through boosting immunogenic cell death for improved cancer immunotherapy

“…DOX has been investigated for the ICD induction of tumor cells [ 45 ]. For example, chimeric polypeptide-conjugated DOX nanoparticles promoted IFN-γ secretion, facilitated the intratumoral infiltration of CD8 + T cells by ICD induction and more efficiently reduced tumor size than did DOX administered alone [ 46 ].…”