Involvement of lysosomal proteins in morphology-driven toxicity of (nano)fibers

Area of Science:

• Nanotoxicology
• Cellular Biology
• Materials Science

Background:

• Fiber morphology (length > 5 µm; respirable diameter < 3 µm) and biopersistence are linked to fibrosis, lung cancer, and mesothelioma.
• Frustrated phagocytosis occurs when macrophages fail to internalize long, rigid fibers, potentially leading to toxicity.
• Nanofiber entanglement can alter morphology and toxicological potential, necessitating careful assessment.

Purpose of the Study:

• To review in vitro studies on macrophage responses to carbon-based nanomaterials with distinct morphologies.
• To reconcile conflicting observations regarding the role of cathepsin B in nanofiber-induced inflammation.
• To discuss limitations of current in vitro models and evaluate approaches for assessing nanofiber toxicity.

Main Methods:

• Assessment of in vitro macrophage responses to carbon-based nanomaterials.
• Analysis of studies investigating cathepsin B translocation and lysosomal enzyme activity.
• Evaluation of existing in vitro models for nanotoxicology.

Main Results:

• Long, rigid carbon nanofibers induce inflammation via cathepsin B translocation from lysosomes.
• Entanglement of nanofibers may reduce their toxicological potential by altering morphology.
• Conflicting data exists on cathepsin B's role, highlighting the need for mechanistic understanding.

Conclusions:

• Nanofiber morphology critically influences toxicological outcomes, particularly through frustrated phagocytosis.
• In vitro models are essential for evaluating nanotoxicology, but current limitations need addressing.
• Further research is needed to refine in vitro methods for accurate nanofiber risk assessment.