Recently, I have observed that one of our synthesized nanoparticles show toxicity in cancer cells at a particular concentration but not in normal cells at that concentration.
This is also what we obtain in our experiments. Cancer cells are usually more sensitive to cytotoxic compounds (including some NPs) then normal cells. This could be attributed to the fact that cancer cells are ususally proliferating at higher rates in cell cultures than normal cells. This is also the basics of current chemotherapy - cytotoxic drugs affect generally proliferating cells (cancer cells, stem cells in bone marrow, rapidly renewing epithelia) than normal cells. Internalization rate of NPs in the different cells could also be a reason (it should be checked).
Anyway, I strongly recommend comparison of cytotoxicity of NPs in cancer cells and stem cells (although comparisons cancer cells-normal cells is quite popular, but quite trivial, I think). Stem cells and cancer cells share many common metabolic features and there it less likely to obtain difference in cytotoxicty.
Did you check or quantify the uptake rate and extent in the two types of cells? Concentration maybe same but the amount taken up by the two types of cells is what will dictate the toxicity, which may (for some reason) differ.
This is also what we obtain in our experiments. Cancer cells are usually more sensitive to cytotoxic compounds (including some NPs) then normal cells. This could be attributed to the fact that cancer cells are ususally proliferating at higher rates in cell cultures than normal cells. This is also the basics of current chemotherapy - cytotoxic drugs affect generally proliferating cells (cancer cells, stem cells in bone marrow, rapidly renewing epithelia) than normal cells. Internalization rate of NPs in the different cells could also be a reason (it should be checked).
Anyway, I strongly recommend comparison of cytotoxicity of NPs in cancer cells and stem cells (although comparisons cancer cells-normal cells is quite popular, but quite trivial, I think). Stem cells and cancer cells share many common metabolic features and there it less likely to obtain difference in cytotoxicty.
1) The general toxicity of nanoparticles is mainly caused by oxidative stress and inflammatory cytokine production.
2) Usually cancerous cells are more sensitive to exogenous oxidative stress than normal cells.
3) Moreover, some nanoparticles demonstrate pH-dependent redox-properties: for instance, nanoceria is pro-oxidant in acidic media, but anti-oxidant in neutral and alcali ones.
4) Due to anaerobic respiration that occurs in the cytosol (lactic acid fermentation) rather than oxidative phosphorylation in the mitochondria (the Warburg effect), cancer cells for energy express increased glycolysis. It is known that the pH value of the medium in a tumour is decreased.
5) Thus, such pH-sensitive nanoparticles can selectively protect the normal cells (unlike malignant) from the oxidative stress.
I am not quite sure that the Warburg effect (and therefore the pH) is a universal characteristic of cancer cells. There at least two reasons for this:
1) There are cancer cells that do not increase anaerobic respiration and glycosis consumption, such as in the case of prostate cancer (that is why prostate cancer metastses can not be reliably detected by PET scan);
2) Pluripotent stem cells (which are otherwise quite normal) apear to use anaerobic glycololys rather than oxidative phosphorilation, similar to cancer cells:
You are right, the Warburg effect is not universal. Also you are right about the buffers. However, the question was about pH-modulated cytotoxicity in cancer cells. Moreover, even in vitro the redox-selectivity of nanoparticles allows to protect normal and to destroy malignant cells. For instance see here.
Dr. Georgi Yordanov described well about the NPs in the presence of different cells. Are there any diffrence concentration of solution in diffrent cells ? If there are specific ph level at normal cells or, in case of cencer cells then the NPs entrapments are different. So the drug delivery depens on the same theory.
Thanks for all the valuable comments. I will surely check the nanoparticle uptake in cancer as well as normal cells. (Georgi Yordanov, Hemant Motiram Vishwasrao )
# A. B. Shcherbakov: In our case also we have observed the nanoparticle toxicty by ROS production and oxidative stress. I think your explanation may be the possible one.
# Wensen Jiang: We have used green chemistry synthesized silver nanoparticles.
'Potential Theranostics Application of Bio-Synthesized Silver Nanoparticles (4-in-1 System)'
Finally, although pH of cancer and normal cells are different. The effect of it towards in vitro systems might not be that much prominent. But in case of living systems it may regulate the nano-toxicty. Anywayz, thanks to discuss. Please send me any good reference link if anyone have. :)
pH alteration could be induced more nanoparticles aggregation in particular cells. in other word, the nanoparticle aggregation produce more ions than normal condition
i am sometimes personally intrigued if parameters like local cellular fluxes where pH may be a contributing factor, brownian movement, etc could play a role in a physiological outcome. Also like some of the above scientists, yes tumor cells show very high sensitivity to external factors; i have experience working with glioma cell lines as well as fibroblasts - something as simple as bacterial contamination or fungal triggers an immediate detachment in the tumor cell lines as compared to fibroblasts - sensitivity!