Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia...

Area of Science:

• Nanomedicine
• Immunology
• Biochemistry

Background:

• Protein corona formation on nanomaterials influences their biological interactions.
• Understanding nanoparticle-protein corona interactions is crucial for developing effective nanotherapies.
• The immune effects of protein corona in acute myeloid leukemia (AML) immunotherapy remain unclear.

Purpose of the Study:

• To investigate the protein corona formation mechanism and immune regulatory effects of iron oxide nanoparticles (IONPs) in AML mouse models.
• To explore how different surface modifications on IONPs impact immune responses.
• To identify potential therapeutic strategies for AML using surface-engineered IONPs.

Main Methods:

• Utilized commercialized iron oxide nanoparticles (IONPs) with varying surface modifications, including carboxymethyl dextran (IONP-COOH) and aminated dextran coatings.
• Employed mouse models with depleted macrophages or knockout of Complement Component 3 (C3).
• Analyzed immune responses, phagocytosis by macrophages, and complement pathway activation (alternative and lectin pathways).

Main Results:

• IONP-COOH demonstrated a reduction in leukemia burden in AML mouse models.
• IONP-COOH activated the complement alternative pathway, leading to C3b binding and enhanced macrophage phagocytosis.
• Aminated dextran-coated IONPs directly absorbed C3b, activated the lectin pathway, and resulted in immune cell exhaustion.

Conclusions:

• Surface chemistry of IONPs critically dictates their immune effects and therapeutic potential in AML.
• IONP-COOH shows promise as an immune activator for AML treatment by leveraging complement-mediated phagocytosis.
• Tailoring nanoparticle surface modifications offers a viable strategy for developing advanced immunotherapies.