Predictive Screening of Ta₄C₃ MXene as an Inhalable Nanotherapeutic Based on an Advanced 3D Air-Liquid Interface Lung...

Area of Science:

• Nanomedicine
• Pulmonary Toxicology
• 3D Cell Culture Models

Background:

• Two-dimensional (2D) MXenes show promise but their pulmonary safety is poorly understood, hindering clinical use.
• Traditional 2D cell cultures provide inconsistent data for assessing nanomedicine safety.
• A physiologically relevant model is needed for predictive screening of MXenes.

Purpose of the Study:

• To develop and validate an immunocompetent 3D alveolar model for pulmonary safety and therapeutic assessment of MXenes.
• To investigate the therapeutic potential of synthesized Ta4C3 MXene nanosheets.
• To evaluate the impact of MXene size on pulmonary responses and therapeutic efficacy.

Main Methods:

• Established a 3D alveolar model using A549 epithelial cells, MRC-5 fibroblasts, and THP-1 macrophages at the air-liquid interface.
• Synthesized and fractionated Ta4C3 MXene nanosheets by size (100-500 nm, 500-2000 nm, ≥2000 nm).
• Assessed MXene biocompatibility, cellular internalization (cryo-TEM, EDX), ROS scavenging, and macrophage polarization (M1/M2).

Main Results:

• The 3D model responded to MXene exposure by showing inflammation and fibrosis markers.
• All Ta4C3 MXene fractions exhibited high biocompatibility and cellular uptake.
• The 100-500 nm Ta4C3 MXene fraction demonstrated potent ROS scavenging, M2 macrophage polarization, and fibrotic remodeling arrest.

Conclusions:

• The developed 3D alveolar model provides a physiologically relevant platform for predictive nanomedicine screening.
• Ta4C3 MXenes, particularly the 100-500 nm fraction, show therapeutic potential for lung inflammation and fibrosis.
• This model enables sensitive detection of anti-inflammatory and anti-fibrotic effects, facilitating MXene clinical translation.