Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis

碳酸钙纳米粒子刺激肿瘤代谢重编程并调节肿瘤转移

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作者: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 D Pagel, Pratim Biswas, Samuel Achilefu

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 &

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.

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.

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