*3.6. Summary*

In summary, we have shown in this study that PNP are taken up in part by macropinocytosis into A549 cells. Egress of PNP from A549 cells is slow and not regulated by increased cytosolic [Ca2<sup>+</sup>]. Intracellular presence of NP (PNP or PM0.2) activates autophagy, delivering the cargo (i.e., PNP or PM0.2) to lysosomes. Lysosomes become dysfunctional due to the presence of NP in lysosomes. NP exposure of A549 cells induces cellular stress (e.g., increased LMP index) without causing mitochondrial dysfunction(s). Further understanding of the cascade of events in cellular stress caused by NP exposure might help devise approaches to mitigation of cellular/organellar damage and pathogenesis of lung diseases (e.g., pulmonary emphysema and/or fibrosis) caused by chronic intermittent low-level NP exposure. Insights into the differences in the interactions of NP with A549 cells versus those with primary AEC may be useful in devising improved nanoparticle-based therapeutic approaches to lung cancer management.

### **4. Materials and Methods**
