## 3 Results and Discussion
### Discussion
Nevertheless, it is also plausible that the differential behavior of PEGylated SWCNTs vs. CQDs is due, at least in part, to the PEG cover, because it has been demonstrated that this polymer interacts with serum components, such as albumin, and that this interaction modifies its stability [32]. Notwithstanding this, it is clearly established that not only the surface but also the core of NPs is an important determinant of toxicity [33]. Thus, it has been consistently shown that the cadmium core of SQDs is extremely toxic and generates DNA damage, oxidative stress by reactive oxygen species production, and cell death [6; 34; 35; 36; 33]. In accordance with these observations are our comparative studies in 3T3-L1 cells demonstrating that SQDs exhibited higher toxicity than CQDs, both in terms ofthreshold dose level and the extent of cell death. Furthermore, SQDs toxicity significantly increased in the presence of serum. This was also observed, though to a lower extent, for CQDs and could be accounted for by enhanced particle incorporation in serum-containing media. Synthetic characteristics of nanodots experience changes when the nanomaterials meet an extracellular environment, acquiring a biological identity that cannot be solely attributed to their synthetic identity [37]. Thus, it has been shown that the presence of serum alters the size and zeta potential of NPs [38]. Our results indicate that microenvironmental factors may modify the synthetic identity of CQDs and SQDs, thus providing a distinct biological identity that influences the response of cells to these particles. Our comparative study of the effect of MEM, DMEM, and FBS on the fluorescence properties of SQDs and CQDs suggested that, in spite of sharing identical surface composition, the former may act as electron donors and become more positive when exposed to DMEM and FBS, while CQDs would behave as electronegative elements under these conditions. Regardless of the field of biological or biomedical application of NPs, it is important to assess the responses of target cells to the specific type of particles to be employed. However, there are few comparative studies addressing whether different cell types may exhibit distinct responses to a given nanoparticle [34; 39; 40; 41]. A meta-analysis of the cellular toxicity of quantum dots revealed that epithelial cells and fibroblasts, of human or murine origin, represent the cell types most employed in nanotoxicity studies [42]. In contrast, toxicological studies of NPs in hepatocytes are very limited (3%, according to the meta-analysis by [PERSON] et al. [42]), even though these cells, which constitute nearly 80% of the liver volume, are key regulators of processes as important as metabolism, detoxification, or innate immunity activation, and are major players in liver pathologies, such as hepatic steatosis or cancer [43; 44]. As compared to 3T3-L1 fibroblasts, high doses of CQDs (400 mg\(\cdot\)L\({}^{-1}\)) were required to trigger cell toxicity in HepG2 hepatocytes. These results refer to cells cultured in the presence of serum, because cell viability was dramatically compromised when HepG2 cells were serum-deprived, while these conditions did not significantly alter 3T3-L1 cell viability. Nevertheless, HepG2 cells were as sensitive as 3T3-L1 cells to SQD-induced toxicity, at least at the lowest concentrations tested, although they seem more resistant to high SQD concentrations than fibroblasts. Apart from their different serum-dependency and culture requirements (DMEM for 3T3-L1 cells, MEM for HepG2 cells), it seems likely that NP internalization, intracellular trafficking, and metabolism occur differently in each cell type. In line with this notion, it has been demonstrated that, although both fibroblasts and liver cell lines internalize gold NPs through clathrin-mediated endocytosis, they show dissimilar responses to endocytosis inhibitors targeting distinctive parts of this pathway [45].