Are cancer cells more negatively charged than healthy cells? Does this hold across cancer types and tissues?

If so, this could prove extremely useful as a broad-spectrum cancer treatment. Simply bond something toxic to cancer cells (such as a chemotherapy drug) to a positively charged nanoparticle, and you can deliver targeted drugs that kill cancer cells but not healthy cells.

Electrophoretic Mobility

Cells in suspension in an electrolyte solution like saline normally have a negative surface charge and can therefore be induced to flow along an electrochemical gradient.

Cell electrophoretic mobility – the ratio of cell velocity to electric field strength, in cm^2 V^(-1) s^(-1) – depends on the cell cycle stage, peaking around mitosis. So you might expect all rapidly dividing cells, including tumor cells, to have high electrophoretic mobility more of the time.[1][4]

In samples from healthy patients and patients with chronic lymphocytic leukemia, n = 19, electrophoretic mobility did not significantly differ between cancer and normal lymphocytes.[2]

In a study of blood cells taken from 700 patients (some healthy, some with various diseases including both blood cancers and solid tumors), all cancers significantly _reduced _the electrophoretic mobility of red blood cells, indicating that the RBCs became less negatively charged. Benign tumors had no effect.[3]

Leukaemic mouse lymphocytes in saline had significantly lower electrophoretic mobility than normal mouse lymphocytes.[5]

In a study of multiple human tumor samples, epithelial tumor cells did not have higher electrophoretic mobility than normal cells, but connective tissue tumor cells (sarcomas and myomas) did.[6]

Another study on different cell lines found that an epithelial cancer cell line (HeLa) was not significantly different in electrophoretic mobility than normal cells, but that a carcinoma cell line (Ehrlich ascites tumor) had significantly higher electrophoretic mobility.[7]

At physiologic pH, breast cancer cells have higher electrophoretic mobility (and thus more negative surface charge) than healthy fibroblasts.[13]

Hamster kidney and liver tumor cells, which are carcinomas, have significantly higher electrophoretic mobility than their healthy counterparts. The MCIM sarcoma becomes more electrophoretically mobile as it gets closer to metastasis.[14]

Solid tumor cells are also less adhesive than healthy cells from the same tissue type; this is what you would expect if they were more negatively charged and thus repelled each other electrostatically more. Blood cells, healthy or cancerous, are already not very adhesive, and accordingly they are more electrostatically mobile.[14]

Electrically Charged Nanoparticle Aggregation

Electrophoresis may not be an accurate way to measure cell surface charge. Voltages necessary to move cells are high, which will change cell function. An alternative method is to create charged nanoparticles and observe which cells they cluster around.

Iron oxide nanoparticles can be given a positive or negative electric charge. If these are introduced into cell culture suspension and they bind to the cells, the bound cells can be captured by applying a magnetic field to one side of the vessel.

Positive nanoparticle binding (as measured by % of cells captured by a magnetic field) is increasing with glucose concentration and lactic acid concentration, and decreasing with concentration of glycolysis inhibitors like DCA and 3BP, suggesting that cells undergoing glycolysis are more negatively charged.[8] Out of 22 cancer cell culture lines and 4 healthy cell lines, all cancer samples had over 50% capture by a magnetic field when mixed with positive nanoparticles; no healthy cell lines had any capture by a magnetic field when mixed with positive nanoparticles.[8]

Positively charged iron oxide nanoparticles, but not negatively charged ones, were observed to aggregate around cancer cells in buffer solution. At high cell concentrations, 99% of cells can by captured by attracting the positively charged nanoparticles in a magnetic field. If blood is spiked with cancer cells, over 70% of the cancer cells can be captured in the same way.[9]

In a mouse model of sarcoma[9], taking a blood sample and mixing it with positive iron oxide nanoparticles and then capturing cells with a magnetic field results in 75.8 circulating tumor cells per 100 uL being captured in the sarcoma mouse, while no cells were captured in healthy controls.

Zinc oxide nanoparticles have a positive surface charge at physiologic pH. These particles have a cytotoxic effect in vitro on multiple cancer cell lines, and in particular cancer cells of lymphocytic lineage are 28-35 times as susceptible to death when treated with ZnO nanoparticles than their non-cancerous counterparts. This is a specificity ratio much higher than that for conventional chemotherapeutic drugs.[10]

Positively charged gold nanoparticles adhere 117 times more strongly to the surface of HeLa cancer cells than negatively charged gold nanoparticles.[11]

Positively charged magnetite nanoparticles have higher uptake into breast cancer cells than negatively charged nanoparticles; but there is no charge-based difference in uptake on healthy embryonic cord cells.[12]


[1]Akagi, Takanori, and Takanori Ichiki. “Cell electrophoresis on a chip: what can we know from the changes in electrophoretic mobility?.” Analytical and bioanalytical chemistry 391.7 (2008): 2433-2441.

[2]Lichtman, Marshall A., and Robert I. Weed. “Electrophoretic mobility and N-acetyl neuraminic acid content of human normal and leukemic lymphocytes and granulocytes.” Blood 35.1 (1970): 12-22.

[3]Rottino, Antonio, and John Angers. “The electrophoretic mobility of erythrocytes in carcinoma and other diseases.” Cancer research 21.10 (1961): 1445-1449.

[4]Mayhew, E. “Cellular electrophoretic mobility and the mitotic cycle.” The Journal of general physiology 49.4 (1966): 717-725.

[5]Cook, G. M. W., and W. Jacobson. “The electrophoretic mobility of normal and leukaemic cells of mice.” Biochemical Journal 107.4 (1968): 549-557.

[6]Vassar, Philip S. “Electrophoretic mobility of human tumour cells.” Nature 197.4873 (1963): 1215-1216.

[7]Simon-Reuss, I., et al. “Electrophoretic studies on some types of mammalian tissue cell.” Cancer research 24.11 Part 1 (1964): 2038-2043.

[8]Chen, Bingdi, et al. “Targeting negative surface charges of cancer cells by multifunctional nanoprobes.” Theranostics 6.11 (2016): 1887.

[9]Li, Zhiming, Jun Ruan, and Xuan Zhuang. “Effective capture of circulating tumor cells from an S180-bearing mouse model using electrically charged magnetic nanoparticles.” Journal of nanobiotechnology 17.1 (2019): 1-9

[10]Rasmussen, John W., et al. “Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications.” Expert opinion on drug delivery 7.9 (2010): 1063-1077..

[11]Peter, Beatrix, et al. “Interaction of positively charged gold nanoparticles with cancer cells monitored by an in situ label-free optical biosensor and transmission electron microscopy.” ACS applied materials & interfaces 10.32 (2018): 26841-26850.

[12]Osaka, Tetsuya, et al. “Effect of surface charge of magnetite nanoparticles on their internalization into breast cancer and umbilical vein endothelial cells.” Colloids and Surfaces B: Biointerfaces 71.2 (2009): 325-330.

[13]Dobrzyńska, Izabela, Elżbieta Skrzydlewska, and Zbigniew A. Figaszewski. “Changes in electric properties of human breast cancer cells.” The Journal of membrane biology 246.2 (2013): 161-166.

[14]Abercrombie, M., and E. J. Ambrose. “The surface properties of cancer cells: a review.” Cancer research 22.5 Part 1 (1962): 525-548.