Iron Oxide Nanoparticles Engineered Macrophage-Derived Exosomes for Targeted Pathological Angiogenesis Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunotherapy

Background:

• Exosome engineering often damages their structure and cargo.
• Pathological angiogenesis requires novel therapeutic strategies.
• Macrophage-based bioreactors offer a promising avenue for exosome modification.

Purpose of the Study:

• To engineer exosomes with magnetic imaging, ferroptosis-inducing, and immunotherapeutic properties for pathological angiogenesis.
• To utilize macrophages as bioreactors for exosome fabrication.
• To evaluate the efficacy and safety of engineered exosomes in targeting pathological angiogenesis.

Main Methods:

• M1-polarized macrophages were induced with extremely small iron oxide nanoparticles (ESIONPs).
• ESIONPs-incorporated exosomes (ESIONPs@EXO) were isolated from macrophage secretions.
• In vitro and in vivo studies were conducted to assess ESIONPs@EXO efficacy and toxicity.
• Magnetic resonance imaging (MRI) was used to evaluate targeting and contrast properties.

Main Results:

• ESIONPs@EXO were successfully fabricated using macrophages as bioreactors.
• ESIONPs@EXO demonstrated significant suppression of pathological angiogenesis both in vitro and in vivo.
• No observable toxicity was associated with ESIONPs@EXO treatment.
• ESIONPs@EXO exhibited excellent T1-weighted contrast for MRI, enabling targeted imaging of pathological angiogenesis.
• Mechanistic studies revealed ferroptosis induction and immunotherapeutic effects of ESIONPs@EXO.

Conclusions:

• A simple, biological method using macrophages engineered ESIONPs@EXO for targeted pathological angiogenesis therapy.
• ESIONPs@EXO show potential as a theranostic agent, combining therapeutic effects with diagnostic imaging capabilities.
• This macrophage-based exosome engineering approach offers a non-toxic and effective strategy for treating pathological angiogenesis.