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The presence of magnetic nanoparticles (NPs) in physiological systems induces toxicity through its effects on mitochondrial function and reactive oxygen species (ROS) imbalance. Magnetic NP induced cytotoxicity has been elaborately evaluated for impending threats, however, a detailed investigation is lacking. It is shown that the interaction of Fe3O4 NPs with cytochrome c can lead to different events based on the NPs to protein ratio, the solution conditions, and the type of surface protection. At low NPs concentration, rapid binding and subsequent electron transfer are the preferred events while at higher concentration slow oxidative modification of the protein is initiated. The slow event of protein modification yields conformational disorientation, loss of stability, and formation of amyloid-like structures with cytochrome c. The possibility that the NP induced oxidative stress and age can work in concert to compromise different aspects of cellular quality control processes is discussed. Suitable surface modifications of the NPs inhibit their direct binding to the protein molecules and minimize NP induced toxicity. [ABSTRACT FROM AUTHOR]

The image shows the major findings of Goutam De, Krishnananda Chattopadhyay, and coworkers, who studied the interaction between iron oxide nanoparticles and cytochrome c, as reported on page 683. The triangle at the top left shows the binding of the protein onto the surface of the bare particles forming amyloid fibrils (transmission electron microscopy image is shown in the background). Appropriate surface modification inhibits protein binding and amyloid formation (shown in the triangle at the bottom right). [ABSTRACT FROM AUTHOR]