Calcium carbonate nanoparticles stimulate cancer cell reprogramming to suppress tumor growth and invasion in an organ-on-a-chip system

The acidic microenvironment of solid tumors induces the propagation of highly invasive and metastatic phenotypes. However, simulating these conditions in animal models present challenges that confound the effects of pH modulators on tumor progression. To recapitulate the tumor microenvironment and isolate the effect of pH on tumor viability, we developed a bifurcated microfluidic device that supports two different cell environments for direct comparison. RFP-expressing breast cancer cells (MDA-MB-231) were cultured in treatment and control chambers surrounded by fibrin, which received acid-neutralizing CaCO3 nanoparticles (nanoCaCO(3)) and cell culture media, respectively. Data analysis revealed that nanoCaCO(3) buffered the pH within the normal physiological range and inhibited tumor cell proliferation compared to the untreated control (p<0.05). Co-incubation of cancer cells and fibroblasts, followed by nanoCaCO(3) treatment showed that the nanoparticles selectively inhibited the growth of the MDA-MB-231 cells and reduced cellular migration of these cells with no impact on the fibroblasts. Sustainable decrease in the intracellular pH of cancer cells treated with nanoCaCO(3) indicates that the extracellular pH induced cellular metabolic reprogramming. These results suggest that the nanoCaCO(3) can restrict the aggressiveness of tumor cells without affecting the growth and behavior of the surrounding stromal cells.

Automated summary

A microfluidic device was developed to simulate the acidic microenvironment of solid tumors, showing that pH modulation with nanoCaCO(3) can inhibit breast cancer cell proliferation and migration selectively. The nanoparticles decreased intracellular pH of cancer cells and limited their aggressiveness without affecting the growth and behavior of surrounding stromal cells.