## 4 Conclusions  
The importance of performing a reliable comparison of toxicological effects of emerging fluorescent carbon nanodots is outlined and described by parallel in vitro cell viability studies. Therefore, fully reliable results were obtained from a comparison of two diverse fluorescent nanodots (various core nature) with similar characteristics (e.g., size, morphology, surface functionalities, etc.) in diverse cell types and in the presence or absence of serum, amongst other variables. The overall result corroborates the obvious prediction about the higher toxicity of SQDs compared to similarly sized-superficial CQDs; however, our comparative studies confirm differentiated cell type-specific responses in carbon-based and semiconductor nanoparticles, establishing that the toxicity levels are dependent on the cell type, the extracellular culture media, and even the presence of other substances or NPs. Our present findings further support the notion previously gained using PEGylated SWCNTs on the modulatory effect of serum proteins on nanotoxicity. For this, the use of fluorescent graphitic NPs to replace conventional dyes is a great added value of nanomedicine. **Supplementary Materials:** The following are available online at [[http://www.mdpi.com/2076-3417/10/24/8845/s1](http://www.mdpi.com/2076-3417/10/24/8845/s1)]([http://www.mdpi.com/2076-3417/10/24/8845/s1](http://www.mdpi.com/2076-3417/10/24/8845/s1)), Figure S1: Emission spectra of SQDs at different excitation wavelengths. [SQDs] = 200 mg-L\({}^{-1}\); slit widths set at 3 nm; Figure S2: Fluorescence quenching of SQDs in presence of CQDs in a 1:1 ratio upon excitation at 390 nm. [Nanodots] = 200 mg-L\({}^{-1}\); slit widths at 3 nm. Figure S3: Confocal microscopy images obtained from 3T3-L1 cells cultured exposed to 0.2 mg-L\({}^{-1}\) SQDs in the absence of serum for 24 h. Control cells were cultured in medium (DMEM) alone. Nuclei (blue) were stained with DAPI. Figure S4: Fluorescence emission in 3T3-L1 cell cultures exposed for 1 h to increasing concentration of CQDs in the absence of serum. Control cells were cultured in medium (DMEM) alone. Measurements were carried out at fluorescence excitation wavelength of 365 nm and emission wavelength of 450 nm. Data (mean \(\pm\) SEM of at least three independent experiments with three replicate wells per treatment) were analyzed by one-way ANOVA multiple comparison test followed by [PERSON]'s LSD test. Significant differences are indicated as ***\(p<0.001\) vs. control. Figure S5. Fluorescence emission in 3T3-L1 cell cultures exposed for 1 h to increasing concentration of CQDs in the absence of serum. Control cells were cultured in medium (DMEM) alone. Measurements were carried out at fluorescence excitation wavelength of 365 nm and emission wavelength of 450 nm. Data (mean \(\pm\) SEM of at least three independent experiments with three replicate wells per treatment) were analyzed by one-way ANOVA multiple comparison test followed by [PERSON]'s LSD test. Figure S6: Cell viability data in HepG2 cells cultured in the presence of decreasing concentrations of FBS (10-0%) for 24 h. Cell viability was measured by the MTT assay. Figure S7. Study of the fluorescence intensity of CQDs exposed to DMEM + 10% FBS. Lines represent fluorescence measurements at different time points [CQDs] = 50 mg-L\({}^{-1}\); slit width at 6 nm. **Author Contributions:** Conceptualization: M.L.S., M.M.M., and M.V. ; methodology: R.G.-R.; synthesis and characterization: A.C. and M.L.S. ; investigation: A.C., M.C.N.-R., and R.G.-R.; resources: M.M.M. and M.V. ; writing--original draft preparation: all authors; writing--review and editing: M.L.S., M.M.M, and M.V. All authors have read and agreed to the published version of the manuscript. **Funding:** We acknowledge support from the Spanish Ministry of Science and Innovation for funding the project NANOMIN (CTQ2014-52939-R), Plan Propio de Investigacion de la Universidad de Cordoba, MINECO/FEDER (BFU2013-44229-R; BFU2016-76711-R; BFU2017-90578-REDT to M.M.M.