Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis.

Aim: CaCO ₃ nanoparticles (nano-CaCO ₃ ) can neutralize the acidic pHe of solid tumors, but the lack of intrinsic imaging signal precludes noninvasive monitoring of pH-perturbation in tumor microenvironment. We aim to develop a theranostic version of nano-CaCO ₃ to noninvasively monitor pH modulation and subsequent tumor response.
Materials & Methods: We synthesized ferromagnetic core coated with CaCO ₃ (magnetite CaCO ₃ ). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murine fibrosarcoma and breast cancer models.
Results: Magnetite CaCO ₃ -MRI imaging showed that nano-CaCO ₃ rapidly raised tumor pHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO ₃ infusion could inhibit metastasis.
Conclusion: Nano-CaCO ₃ exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.