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 D. Pagel; Pratim Biswas; Samuel Achilefu

doi:10.2217/nnm-2018-0302

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 D. Pagel, Pratim Biswas, Samuel Achilefu

Research output: Contribution to journal › Article › peer-review

19 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 language	English (US)
Pages (from-to)	169-182
Number of pages	14
Journal	Nanomedicine
Volume	14
Issue number	2
DOIs	https://doi.org/10.2217/nnm-2018-0302
State	Published - Jan 1 2019
Externally published	Yes

Keywords

MRI
magnetite
nano-CaCO
pH modulation
theranostic

ASJC Scopus subject areas

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

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10.2217/nnm-2018-0302

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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. D., 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

Som, A, Raliya, R, Paranandi, K, High, RA, Reed, N, Beeman, SC, Brandenburg, M, Sudlow, G, Prior, JL, Akers, W, Mah-Som, AY, Habimana-Griffin, L, Garbow, J, Ippolito, JE, Pagel, MD, Biswas, P & Achilefu, S 2019, 'Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis', Nanomedicine, vol. 14, no. 2, pp. 169-182. https://doi.org/10.2217/nnm-2018-0302

@article{e9a7df2a34424dbaa6e01ea2e87cd90d,

title = "Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis",

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.",

keywords = "MRI, magnetite, nano-CaCO, pH modulation, theranostic",

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

note = "Funding Information: A Som was supported by the NCI F30CA189435-03 and NIH training Grant Number T32 GM07200. R Raliya, L Habimana-Griffin and N Reed were supported by NIH-NCI U54CA199092. AY Mah-Som was supported by NIAID 1F30AI129110 and NIH training Grant Number T32 GM07200. WJ Akers was supported by NCI R50 CA211481. JL Prior was supported by NIH P50 CA094056 (Molecular Imaging Center) and NCI P30 CA091842 (Siteman Cancer Center Small Animal Cancer Imaging shared resource). The study was funded in part by grants from the National Institutes of Health (U54 CA199092, R01 EB021048, R01 CA171651, P50 CA094056, P30 CA091842, S10 OD016237, S10 RR031625 and S10 OD020129), Department of Defense Breast Cancer Research Program (W81XWH-16-1-0286), and the Alvin J Siteman Cancer Research Fund (11-FY16-01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: {\textcopyright} 2019 2018 Future Medicine Ltd.",

year = "2019",

month = jan,

day = "1",

doi = "10.2217/nnm-2018-0302",

language = "English (US)",

volume = "14",

pages = "169--182",

journal = "Nanomedicine",

issn = "1743-5889",

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T1 - Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis

AU - Som, Avik

AU - Raliya, Ramesh

AU - Paranandi, Krishna

AU - High, Rachel A.

AU - Reed, Nathan

AU - Beeman, Scott C.

AU - Brandenburg, Matthew

AU - Sudlow, Gail

AU - Prior, Julie L.

AU - Akers, Walter

AU - Mah-Som, Annelise Y.

AU - Habimana-Griffin, Lemoyne

AU - Garbow, Joel

AU - Ippolito, Joseph E.

AU - Pagel, Mark D.

AU - Biswas, Pratim

AU - Achilefu, Samuel

N1 - Funding Information: A Som was supported by the NCI F30CA189435-03 and NIH training Grant Number T32 GM07200. R Raliya, L Habimana-Griffin and N Reed were supported by NIH-NCI U54CA199092. AY Mah-Som was supported by NIAID 1F30AI129110 and NIH training Grant Number T32 GM07200. WJ Akers was supported by NCI R50 CA211481. JL Prior was supported by NIH P50 CA094056 (Molecular Imaging Center) and NCI P30 CA091842 (Siteman Cancer Center Small Animal Cancer Imaging shared resource). The study was funded in part by grants from the National Institutes of Health (U54 CA199092, R01 EB021048, R01 CA171651, P50 CA094056, P30 CA091842, S10 OD016237, S10 RR031625 and S10 OD020129), Department of Defense Breast Cancer Research Program (W81XWH-16-1-0286), and the Alvin J Siteman Cancer Research Fund (11-FY16-01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. Publisher Copyright: © 2019 2018 Future Medicine Ltd.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - MRI

KW - magnetite

KW - nano-CaCO

KW - pH modulation

KW - theranostic

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AN - SCOPUS:85059436196

SN - 1743-5889

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JO - Nanomedicine

JF - Nanomedicine

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ER -

Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis

Abstract

Keywords

ASJC Scopus subject areas

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