Reprogramming Immunogenicity of Iron Oxide Nanoparticles through Sulfated Glycan Presentation

Area of Science:

• Biomaterials Science
• Immunology
• Nanotechnology
• Drug Delivery

Background:

• Heparin (HP) and dextran sulfate (DS) possess known anti-thrombotic and immunomodulatory effects.
• A direct comparison of HP- and DS-coated superparamagnetic iron oxide nanoparticles (SPIONs) regarding their immunological responses is currently lacking.
• Understanding these differences is crucial for optimizing SPIONs in drug delivery applications.

Purpose of the Study:

• To evaluate and compare the immunological behavior of HP-SPIONs and DS-SPIONs.
• To assess their effects on complement activation, immune cell activation, and endothelial cell responses.
• To determine their suitability for regenerative medicine versus immunotherapy.

Main Methods:

• In vitro studies using human whole blood, primary immune cells (monocytes, neutrophils, dendritic cells), and endothelial cells.
• In vivo studies in healthy mice to assess systemic immune responses.
• Analysis of complement activation markers (C3bc, C3bBbP, TCC), cell surface markers (CD11b, ICAM-1, CD62P/E), cellular uptake, and macrophage polarization (M1/M2 phenotype).

Main Results:

• Both HP-SPIONs and DS-SPIONs effectively suppressed complement activation, indicating good biocompatibility.
• HP-SPIONs activated monocytes and endothelial cells, suggesting a pro-inflammatory profile.
• DS-SPIONs suppressed endothelial activation, were preferentially taken up by myeloid cells, and induced an immunosuppressive, pro-healing macrophage phenotype.

Conclusions:

• DS-SPIONs exhibit a pro-healing immune profile suitable for regenerative drug delivery.
• HP-SPIONs induce pro-inflammatory responses, potentially beneficial for anticancer immunotherapy.
• The choice of HP or DS coating significantly influences SPION immunological behavior and therapeutic potential.