Nanoparticle Charge

Nanoparticle charge is very important when it comes to delivery within the body. Nanoparticle charge can come from the nanoparticle core or ligand, surface coatings, which can be used to tailor the charge of particles which is explored in an upcoming blog on nanoparticle coatings. Almost always human cells, or rather cell membranes, within our bodies are negatively charged where we want to develop positively charged to have attraction^1,2. However, the interaction is non-specific.

Can we target specific cells using charge?

Due to the non-specific nature of charge and most cells having a negative surface coating, it is difficult to target specific cells. However, certain cells may over-express glycoproteins, a surface protein on cells, which leads to far more negative charged surfaces compared to other cells. One example is cancerous cells within a solid tumour environment. In theory, due to the increased glycoproteins on the surface, positively charged particles will have a higher affinity for the cancerous cells than the healthy cells³.

The issue is cancerous cells develop and evolve over time. One study presented intra-tumour penetration with early-stage benefiting positively surface charged particle penetration and late-stage benefiting negatively surface charged particle penetration⁴.

Why not produce only positive nanoparticles?

Nanoparticles may be designed with a neutral or negative surface charge to avoid cellular uptake for diagnostic applications⁵. The nanoparticles could be designed to react with biomolecules within the blood and produce a quantifiable response.

Conclusion

Nanoparticle charge is very important to consider for nanoparticle penetration and uptake within cells. The charge is important for internalisation, uptake, within cells as well as avoiding cell uptake for a variety of diagnostic and therapeutic applications⁶.

Charge is important when considering additional functionalisation and coatings used on a nanoparticle where changing the charge can have dramatic effects on the penetration and uptake within cells.

References

1. Fröhlich, E. (2012). The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. In International Journal of Nanomedicine (Vol. 7, pp. 5577–5591). Dove Press. https://doi.org/10.2147/IJN.S36111
2. Tatur, S., MacCarini, M., Barker, R., Nelson, A., & Fragneto, G. (2013). Effect of functionalized gold nanoparticles on floating lipid bilayers. Langmuir, 29(22), 6606–6614. https://doi.org/10.1021/la401074y
3. Chen, B., Le, W., Wang, Y., Li, Z., Wang, D., Ren, L., Lin, L., Cui, S., Hu, J. J., Hu, Y., Yang, P., Ewing, R. C., Shi, D., & Cui, Z. (2016). Targeting negative surface charges of cancer cells by multifunctional nanoprobes. Theranostics, 6(11), 1887–1898. https://doi.org/10.7150/thno.16358
4. Han, D., Qi, H., Huang, K., Li, X., Zhan, Q., Zhao, J., Hou, X., Yang, X., Kang, C., & Yuan, X. (2018). The effects of surface charge on the intra-tumor penetration of drug delivery vehicles with tumor progression. Journal of Materials Chemistry B, 6(20), 3331–3339. https://doi.org/10.1039/c8tb00038g
5. Blanco, E., Shen, H., & Ferrari, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. In Nature Biotechnology (Vol. 33, Issue 9, pp. 941–951). NIH Public Access. https://doi.org/10.1038/nbt.3330
6. Sheng, Y., Liu, C., Yuan, Y., Tao, X., Yang, F., Shan, X., Zhou, H., & Xu, F. (2009). Long-circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water-soluble chitosan. Biomaterials, 30(12), 2340–2348. https://doi.org/10.1016/j.biomaterials.2008.12.070