Human Properdin Opsonizes Nanoparticles and Triggers a Potent Pro-inflammatory Response by Macrophages without...

Area of Science:

• Biomedical Engineering
• Immunology
• Materials Science

Background:

• Nanoparticle drug delivery systems are influenced by the complement system, affecting inflammation and clearance.
• Understanding nanoparticle-protein interactions is crucial for effective therapeutic applications.

Purpose of the Study:

• To investigate the interaction between human properdin and functionalized carbon nanotubes (CNTs).
• To determine properdin's role in modulating nanoparticle uptake and immune response.
• To explore the potential of properdin domains as complement inhibitors.

Main Methods:

• Surface functionalization of CNTs (CMC-CNT, Ox-CNT).
• Protein binding assays with human properdin and its TSR4+5 domains.
• Macrophage (THP-1) uptake studies.
• Analysis of pro-inflammatory responses (qRT-PCR, cytokine arrays, NF-κB translocation).
• Complement consumption assays.

Main Results:

• Human properdin binds to functionalized CNTs via its TSR4+5 domains, recognizing surface charge patterns.
• Properdin enhances CMC-CNT uptake by THP-1 macrophages, inducing a pro-inflammatory response.
• Recombinant TSR4+5 inhibits complement consumption by CNTs.

Conclusions:

• Properdin interaction with CNTs is significant, especially in inflammatory environments.
• Nanoparticle decoration with properdin's TSR4+5 domains shows potential for complement inhibition in pathological conditions.