Implementation of a Dynamic Co-Culture Model Abated Silver Nanoparticle Interactions and Nanotoxicological Outcomes...

Area of Science:

• Nanotoxicology
• In vitro toxicology
• Cellular biology

Background:

• Engineered nanoparticles (NPs) are increasingly used in consumer products, necessitating safety evaluations.
• Standard in vitro and in vivo models show discrepancies due to NP reactivity and variable behavior.
• Existing models struggle to accurately predict NP interactions within biological systems.

Purpose of the Study:

• To develop enhanced in vitro models incorporating immune elements and dynamic flow for improved NP safety assessment.
• To investigate the impact of dynamic flow and immune cells on nanoparticle-cellular interactions and toxicity.
• To compare responses in enhanced models versus traditional static cell cultures.

Main Methods:

• Established human alveolar epithelial and macrophage (A549/U937) co-cultures under static and dynamic flow conditions.
• Challenged co-cultures and static A549 models with 10 nm citrate-coated silver nanoparticles (AgNPs).
• Assessed NP-cellular interface, cellular morphology, deposition, toxicity, and stress endpoints (ROS, HSP70, cytokines).

Main Results:

• Dynamic flow altered cellular morphology and reduced AgNP deposition by ~20% compared to static conditions.
• Activated macrophages and dynamic flow mitigated AgNP-induced cellular toxicity and inflammatory responses.
• Observed differential biological responses and AgNP-cellular interface reshaping based on model composition and flow.

Conclusions:

• Enhanced in vitro models with immune components and dynamic flow offer a more physiologically relevant platform for NP safety assessment.
• These advanced models can elucidate novel NP-cellular interactions and provide more accurate toxicological profiles.
• Dynamic flow and immune cell presence significantly influence NP bioeffects, improving predictive toxicology.