In our study, we observed negatively charged particles had more cellular uptake than cationic particles. We have found some reports with the opposite being the case and a handful of other reports with similar results to ours. We want to know more about the mechanism(s) of cellular uptake.
It is clear that for delivery of nanoparticles to heterogeneous tumours,
differences in cellular uptake and sorting can have significant implications. Importantly, the polyvalent surface of nanoparticles may induce cross-linking of cellular receptors, start signalling processes, induce structural alterations
at the cell surface, and interfere with normal cell function. Moreover, when studying cellular uptake of nanoparticles one should keep in mind that the rate of endocytosis may also depend on the cell density.
Researchers found that uptake of gold nanoparticles (NP) (16 nm) modified by positively charged cell-penetrating peptides. Because particles with a positive charge will bind to the negatively charged cell surface, one would expect positively charged particles to be endocytosed more efficiently than negatively charged particles. But, in contrast, a higher uptake of negatively charged nanoparticles has been reported in HEK cells.
Internalization of +ve NPs into cells which is possibly due to the +ve NPs prefer to contact with the negatively charged cell surface via their electrostatic interaction.
Further it is reported that some of +ve NPs could escape from lysosome after being internalized and exhibit perinuclear localization, whereas the negatively and neutrally charged NPs prefer to colocalize with lysosome.
A possible reason was that the abundant positive charge of these NPs could trigger the concurrent influx of chloride ions to maintain charge neutrality,leading to osmotic swelling and physical rupture of the lysosomes, which was well-known as the “proton-sponge” effect.There is another study which proved that +ve charge on HAP could increase cellular uptake compared to -Ve and neutral charged HAP.
Please see the following 3 informative articles on Mechanisms:
http://web.missouri.edu/~leejam/publications/nanotech-Liang.pdf
http://217.219.202.60/documents/10129/37464/Endocytosis%2Band%2Bintracellular%2Btransport%2Bof.pdf
http://www.bfbm.cn/uploadfiles/paper/2011/4.pdf
Thank you Prakash Katakam for your detailed answer to our question. from your response and the attached file we can infer that surface charge of nanoparticles is not the only affecting factor for their cellular uptake, right?
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