Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis

Avik Som, Ramesh Raliya, Krishna Paranandi, Rachel A. High, Nathan Reed, Scott C. Beeman, Matthew Brandenburg, Gail Sudlow, Julie L. Prior, Walter Akers, Annelise Y. Mah-Som, Lemoyne Habimana-Griffin, Joel Garbow, Joseph E. Ippolito, Mark "Marty" Pagel, Pratim Biswas, Samuel Achilefu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Aim: CaCO3 nanoparticles (nano-CaCO3) 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-CaCO3 to noninvasively monitor pH modulation and subsequent tumor response. Materials & methods: We synthesized ferromagnetic core coated with CaCO3 (magnetite CaCO3). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murine fibrosarcoma and breast cancer models. Results: Magnetite CaCO3-MRI imaging showed that nano-CaCO3 rapidly raised tumor pHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO3 infusion could inhibit metastasis. Conclusion: Nano-CaCO3 exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.

Original languageEnglish (US)
Pages (from-to)169-182
Number of pages14
JournalNanomedicine
Volume14
Issue number2
DOIs
StatePublished - Jan 1 2019

Keywords

  • magnetite
  • MRI
  • nano-CaCO
  • pH modulation
  • theranostic

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

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  • Cite this

    Som, A., Raliya, R., Paranandi, K., High, R. A., Reed, N., Beeman, S. C., Brandenburg, M., Sudlow, G., Prior, J. L., Akers, W., Mah-Som, A. Y., Habimana-Griffin, L., Garbow, J., Ippolito, J. E., Pagel, M. M., Biswas, P., & Achilefu, S. (2019). Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis. Nanomedicine, 14(2), 169-182. https://doi.org/10.2217/nnm-2018-0302