Immunogenic Cell Death For Chemodynamic Therapy-induced Immunotherapy Of Lung Metastasis Of Melanoma In Vivo Mediated By Nanoparticles Loaded With Iron-carbonyl Complex

Malignant melanoma（MM）is a malignant tumor derived from melanocytes of the skin,which was easily spread to lymph nodes,liver,lung,brain and other organs.Lung is the most common site of distant metastases.Therefore,effective treat strategies are needed to be developed for improving the survival of lung metastasis of melanoma.Immunogenic cell death（ICD）is an increasingly recognized pathway of cell death that was one strategy of cancer immunotherapies,which is more effective than conventional therapies for reducing tumor metastasis and improving prognosis.In this work,a nanoplatform（Fe CORM NPs）,nanoparticles loaded with iron-carbonyl complex was constructed.By exploiting the chemodynamic therapy（CDT）and ICD-induced immunotherapy（IMT）,the nanoparticles exhibited an excellent efficacy against lung metastasis of melanoma in vivo.The iron-carbonyl compound of the nanomaterials could be initiated by both glutathione（GSH）and hydrogen peroxide（H₂O₂）to release CO and generate ferrous iron through ligand exchange and oxidative destruction pathways.The released CO caused mitochondria damage whereas the generated ferrous iron led to oxidative stress via Fenton reaction.On the other hand,the nanomaterials induced ICD-based IMT,which worked jointly with CDT to exhibit excellent effect against the lung metastasis of melanoma through mouse model.This work demonstrated how a nanoplatform,simple and stable but showing excellent efficacy against tumors,could be built by using simple building blocks via self-assembling approach.Importantly,the system took the advantages of relatively high levels of GSH and H₂O₂ in tumors to initiate the therapeutic effects,which rendered the nanoplatform a capability of differentiating normal cells from tumor cells.