Complement opsonization of nanoparticles: Differences between humans and preclinical species.

Area of Science:

• Immunology
• Nanomedicine
• Biomaterials

Background:

• The complement system is vital for nanoparticle clearance.
• Understanding species-specific complement opsonization is key for nanomedicine translation.
• Superparamagnetic iron oxide (SPIO) nanoparticles are widely used in medical imaging and therapy.

Purpose of the Study:

• To investigate the complement protein C3 opsonization pathways and efficiency of SPIO nanoworms in various preclinical species and strains.
• To assess inter-subject and inter-strain variability in C3 opsonization.
• To evaluate the predictive value of animal models for human complement responses to nanoparticles.

Main Methods:

• Studied C3 opsonization of 106 nm SPIO nanoworms in human, dog, rat, and mouse sera.
• Utilized a panel of SPIO nanoparticles with varying sizes and dextran coatings.
• Analyzed complement activation pathways (alternative, lectin, classical) and C3 deposition levels.

Main Results:

• Human C3 opsonization occurred exclusively via the alternative pathway.
• Dog, rat, and mouse C3 opsonization involved Ca2+-dependent pathways (lectin and/or classical).
• Human and dog sera showed high inter-subject variability; rat and mouse sera showed low inter-strain variability.
• Human sera had lower C3 opsonization levels than animal sera.
• Nanoparticle size significantly impacted C3 opsonization, decreasing with smaller sizes.
• Dog and rat sera demonstrated predictive value for human C3 opsonization.

Conclusions:

• Species and strain differences significantly influence nanoparticle complement opsonization.
• Preclinical models require careful selection to accurately predict human responses to nanomedicines.
• Consideration of these variations is essential for successful nanomedicine development and clinical translation.