Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts.

Area of Science:

• Biomedical Engineering
• Immunology
• Nanotechnology

Background:

• Systemic nanomedicine administration activates the complement cascade, leading to immune responses.
• Predicting high complement responders is crucial for nanomedicine safety and efficacy.
• Polyethylene glycol (PEG) and dextran are common polymer coatings that can trigger complement activation.

Purpose of the Study:

• To analyze factors influencing complement activation by PEGylated liposomal doxorubicin (PLD) and dextran-coated superparamagnetic iron oxide nanoworms (SPIO NWs).
• To identify biomarkers predicting high complement activation risk by nanomedicines.

Main Methods:

• Multifaceted analysis of complement activation (C3 deposition) in patient and donor plasma exposed to PLD and SPIO NWs.
• Correlation analysis of complement activation with patient factors (age, inflammation, infection, sex) and plasma biomarkers (complement factors, immunoglobulins).

Main Results:

• Complement activation varied significantly (29-fold for PLD, 26-fold for SPIO NWs).
• Age inversely correlated with complement activation; other factors had minor effects.
• Anti-PEG IgM titers strongly predicted high complement activation by PLD, while anti-dextran antibodies showed weaker correlation for SPIO NWs.
• Nanoparticle-bound immunoglobulins best correlated with and predicted complement activation.

Conclusions:

• Anti-PEG IgM is a key predictive biomarker for high complement activation by PLD.
• Nanoparticle-bound immunoglobulins play a critical role in initiating complement responses.
• Characterizing nanoparticle-binding antibodies is vital for nanomedicine safety and risk stratification.