Figure 4

Cytotoxic effects of NPs. In the biological environment, NPs may trigger the production of reactive oxygen species (ROS). Elevated ROS levels may lead to (i) activation of cellular stress-dependent signaling pathways, (ii) direct damage of subcellular organelles such as mitochondria and (iii) DNA fragmentation in the nucleus, resulting in cell cycle arrest, apoptosis, and inflammatory response. NPs may interact with membrane-bound cellular receptors, e.g., growth factor (GF) receptors and integrins, inducing cellular phenotypes such as proliferation, apoptosis, differentiation, and migration. After internalization via endocytic pathways, NPs are trafficked along the endolysosomal network within vesicles with the help of motor proteins and cytoskeletal structures. To access cytoplasmic or nuclear targets, NPs must escape from the endolysosomal network and traverse through the crowded cytoplasm.