Enhancing immunogenic cell death in lung cancer through Ferritin‐based nanocarriers: a novel approach for combined immunotherapy

Abstract Immunogenic cell death (ICD) represents a crucial mechanism in cancer therapy, providing a pathway to trigger antitumor immune responses. Recent advancements in understanding and applying ICD for lung cancer therapy have identified traditional chemotherapy agents as potent ICD inducers. Despite their efficacy, the systemic toxicity and potential for inducing drug resistance limit their clinical application. This study introduces a novel approach utilizing ferritin‐based nanocarriers [HFn(+)] for the targeted delivery of doxorubicin (DOX), combined with CpG oligodeoxynucleotides as an immune adjuvant, to enhance the immunogenicity and therapeutic efficacy against lung cancer. The engineered HFn(+) nanocarriers exploit the tumor‐targeting ability of ferritin, capitalizing on its preferential uptake via transferrin receptor 1 (TfR1) overexpression on tumor cells. We comprehensively evaluate the preparation, characterization, and in vitro and in vivo efficacy of pHFn(+)@CpG/DOX complexes. The study confirms the potent antitumor activity of pHFn(+)@CpG/DOX in a lung cancer model, presenting a promising strategy for combined tumor immunotherapy with minimal systemic toxicity. This approach not only underscores the potential of nanocarrier‐based drug delivery systems in cancer therapy but also opens new avenues for developing more effective and targeted cancer treatment modalities.