Calcium Carbonate Nanoparticles Stop Cancer by Neutralizing the Tumor Microenvironment

Tumor growth was halted in a mouse cancer model by the injection of novel calcium carbonate nanoparticles that neutralized the pH of the tumor microenvironment.

The acidic extracellular environment of tumors increases their aggressiveness and potential to metastasize, but few methods exist to selectively modulate the extracellular pH of the tumor environment. Transient flushing of biological systems with alkaline fluids or proton pump inhibitors is impractical and nonselective.

Investigators at Washington University (St. Louis, MO, USA) tried a new approach to modulate the pH of the tumor microenvironment. They used two processes, polyethyleneglycol-based diffusion and ethanol-assisted diffusion, to prepare calcium carbonate nanoparticles ranging in size from 20 to 300 microns. The nanoparticles were suspended in an albumin-based solvent that prevented aggregation and allowed them to be injected intravenously into an animal.

The investigators reported in the December 25, 2015, online edition of the journal Nanoscale that by using a mouse cancer model they were able to demonstrate that the selective accumulation of nano-calcium carbonate in tumors increased tumor pH over time, eventually reaching pH 7.4. Daily injections of calcium carbonate nanoparticles halted tumor growth in the mouse fibrosarcoma model, but stopping the injections allowed tumor growth to resume.

"Cancer kills because of metastasis," said Avik Som, a medical and doctoral student in biomedical engineering at Washington University. "The pH of a tumor has been heavily correlated with metastasis. For a cancer cell to get out of the extracellular matrix, or the cells around it, one of the methods it uses is a decreased pH. Calcium and carbonate are both found heavily in the body, and they are generally non-toxic. When calcium carbonate dissolves, the carbonate becomes carbon dioxide and is released through the lungs, and calcium is often incorporated into the bones."

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