期刊
NANOMEDICINE
卷 14, 期 2, 页码 169-182出版社
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2018-0302
关键词
magnetite; MRI; nano-CaCO3; pH modulation; theranostic
资金
- NCI [F30CA189435-03, R50 CA211481, P30 CA091842]
- NIH [T32 GM07200, P50 CA094056]
- NIH-NCI [U54CA199092]
- NIAID [1F30AI129110]
- National Institutes of Health [P30 CA091842, P50 CA094056, U54 CA199092, R01 EB021048, R01 CA171651, S10 OD016237, S10 RR031625, S10 OD020129]
- Department of Defense Breast Cancer Research Program [W81XWH-16-1-0286]
- Alvin J Siteman Cancer Research Fund [11-FY16-01]
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.
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