Graphene oxide–microplastic hybrid showcase elicited discrepancy through intrinsic interaction mediated steatosis, and apoptosis in macrophages

The widespread natural abundance of microplastics (MP) has been recognized to pose significant global health concerns, particularly due to limited understanding of their biological interactions. With the uncontrolled increase in MP accumulation in the environment, their interaction with xenobiotics like nanomaterials used for different biomedical and environmental applications is likely to be enhanced, raising concern over the advanced toxicological impacts. Hence, it is important to deduce their threatening toxicity to the biological niche, including humans. This study deduces the cytotoxicity of a green-synthesized GO@MP hybrid using macrophage cells, integrating experimental and computational methods. Physicochemical characterization was performed using FTIR, SEM, and DLS. Toxicological assessment revealed that GO@MP significantly reduced cell viability, primarily via surface adherence and deposition. Experimental analysis demonstrated concentration-dependent accumulation and internalization of GO and MP. Compared to individual MP and GO, the hybrid induced higher levels of lipid peroxidation and mitochondrial membrane damage, triggering enhanced apoptosis. <i>In silico</i> analysis indicated interactions between GO@MP and proteins involved in oxidative stress and apoptotic pathways for the molecular discrepancies. Computational modelling further unraveled atomic-level interactions between GO and MP with key metabolic and apoptotic proteins, including PEX5, PEX14, BCL2, and Caspase 3. These interactions contributed to structural and functional perturbations in protein regulation, resulting in steatosis, mitochondrial dysfunction, and apoptotic cell death. These findings uncovered the amplified toxic effects of MP combined with GO and underscore the need to consider such interactions in environmental health risk assessments. Furthermore, this study aims to provides critical insights into the mechanistic toxicity of nanomaterial-microplastic hybrids, emphasizing the need for caution in their environmental and biomedical applications.