Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis

CaCO nanoparticles (nano-CaCO ) 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 to noninvasively monitor pH modulation and subse...

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Bibliographic Details
Published in:Nanomedicine (London, England) England), 2019-01, Vol.14 (2), p.169-182
Main Authors: Som, Avik, Raliya, Ramesh, Paranandi, Krishna, High, Rachel A, Reed, Nathan, Beeman, Scott C, Brandenburg, Matthew, Sudlow, Gail, Prior, Julie L, Akers, Walter, Mah-Som, Annelise Y, Habimana-Griffin, Lemoyne, Garbow, Joel, Ippolito, Joseph E, Pagel, Mark D, Biswas, Pratim, Achilefu, Samuel
Format: Article
Language:English
Subjects:
Acids
Animals
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Calcium Carbonate - pharmacology
Cancer therapies
Cell Line, Tumor
Cell Survival - drug effects
Chemotherapy
Ethanol
Female
Fibrosarcoma - drug therapy
Fibrosarcoma - pathology
Humans
Lymphoma
magnetite
Male
Medical imaging
Metabolism
Metastasis
Mice
MRI
Mutation
nano-CaCO
Nanoparticles
Nanoparticles - chemistry
Neoplasm Metastasis - drug therapy
Particle Size
pH modulation
theranostic
Theranostic Nanomedicine
Tumor Microenvironment - drug effects
Tumors
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Summary:CaCO nanoparticles (nano-CaCO ) 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 to noninvasively monitor pH modulation and subsequent tumor response. We synthesized ferromagnetic core coated with CaCO (magnetite CaCO ). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murine fibrosarcoma and breast cancer models. Magnetite CaCO -MRI imaging showed that nano-CaCO rapidly raised tumor pHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO infusion could inhibit metastasis. Nano-CaCO exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.
ISSN:1743-5889
1748-6963
1748-6963
DOI:10.2217/nnm-2018-0302