AML-Targeted Metal-Polyphenol Nanoplatform Induces Ferroptosis-ICD Cascade for Antitumor Immunity Boosting

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Acute Myeloid Leukemia (AML) presents therapeutic challenges due to low immunogenicity and an immunosuppressive tumor microenvironment (iTME).
• Effective drug delivery systems are needed to overcome these challenges in AML treatment.

Purpose of the Study:

• To develop a ferritin-based nanoplatform (Fe-SH@Fn) for targeted co-delivery of shikonin (SH) and Fe3+ in AML.
• To investigate the synergistic effects of ferroptosis and immunogenic cell death (ICD) induction by Fe-SH@Fn in AML.

Main Methods:

• Engineered a ferritin nanoplatform (Fe-SH@Fn) encapsulating shikonin (SH) and Fe3+ for CD71-mediated targeting of AML cells.
• Investigated the disassembly of Fe-SH@Fn within AML cells, leading to Fe2+-driven ferroptosis via Fenton reactions and SH-induced ICD.
• Assessed the impact of Fe-SH@Fn treatment on the tumor microenvironment, including dendritic cell maturation, CD8+ T cell infiltration, and regulatory T cell populations.

Main Results:

• Fe-SH@Fn demonstrated synergistic ferroptosis and ICD induction in AML cells.
• Treatment with Fe-SH@Fn led to significant tumor growth inhibition (81.25%) in a subcutaneous AML model.
• Fe-SH@Fn extended median survival by 2.8-fold in an orthotopic AML model with no observed systemic toxicity.

Conclusions:

• The Fe-SH@Fn nanoplatform offers a translatable strategy to overcome AML immunosuppression.
• Targeted delivery and synergistic ferroptosis-ICD activation represent a promising therapeutic approach for Acute Myeloid Leukemia.