L-Cysteine capped zinc oxide nanoparticles induced cellular response on adenocarcinomic human alveolar basal epithelial cells using a conventional and organ-on-a-chip approach

Zinc oxide nanoparticles (ZnO NPs) are among the well-characterized nanomaterials with multifaceted biomedical applications, including biomedical imaging, drug delivery, and pharmaceutical preparations. The high surface charge of ZnO NPs leads to the agglomeration of the particles. Therefore, surface coating with a suitable ligand can increase colloidal stability. In this present study, in-vitro responses of ZnO NPs capped with a sulfur-containing amino acid, L-cysteine (Cys-ZnO NPs), on A549 cells was investigated. Fourier Transform Infrared Spectroscopy (FTIR) studies were carried out to confirm the capping of ZnO NPs with L-cysteine. Cytotoxic studies using A549 cells demonstrated reduced cytotoxicity in comparison with already reported pristine Zinc Oxide nanoparticles. The cellular uptake is confirmed by fluorescent cytometry. However, a higher concentration (160 µg/mL) of Cys-ZnO NPs led to apoptotic cell death marked by nuclear condensation, mitochondrial membrane depolarization, actin filament condensation, lysosomal damage LDH leakage, intracellular ROS production, blebbing, upregulation of Bax and downregulation of Bcl-2 gene expression. Cys-ZnO NPs treatment was also carried out in cells cultured in a microfluidic lung-on-a-chip device under a physiologically relevant flow rate. The study concluded that the microfluidic-based lung-on-a-chip culture resulted in reduced cell death compared to the conventional condition.