Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood

Area of Science:

• Immunology
• Nanotechnology
• Biomedical Engineering

Background:

• Complement system is key in innate immunity and nanoparticle recognition by immune cells.
• Antibody-targeted iron oxide nanoparticles (CLIO NWs) are used in diagnostics and imaging.
• CLIO NWs target cancer cells but face challenges with immune cell uptake.

Purpose of the Study:

• Investigate the role of complement in the targeting selectivity of antibody-conjugated CLIO NWs for tumor cells in whole blood.
• Determine the impact of complement inhibition on nanoparticle uptake by leukocytes and tumor cell isolation efficiency.

Main Methods:

• Used 60 nm cross-linked iron oxide nanoworms (CLIO NWs) targeting Her2/neu and EpCAM.
• Spiked cancer cells in whole blood and assessed CLIO NWs targeting and magnetic isolation.
• Analyzed complement C3 opsonization pathways and the effect of complement inhibitors (compstatin, soluble CD35, soluble CD55).

Main Results:

• CLIO NWs showed high targeting but low specificity due to leukocyte uptake.
• Complement C3 opsonization occurred mainly via the alternative pathway, higher for antibody-conjugated CLIO NWs.
• Soluble complement inhibitors blocked up to 99% of leukocyte uptake, improving tumor cell isolation selectivity.

Conclusions:

• Complement activation significantly impacts nanoparticle targeting selectivity in whole blood.
• Inhibiting complement pathways enhances the specificity of CLIO NWs for tumor cell isolation.
• Complement therapeutics offer a strategy to improve nanoparticle-based diagnostics and therapeutics.