Mallinckrodt Institute of Radiology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA.
Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO 63130, USA.
Nanomedicine (Lond). 2019 Jan;14(2):169-182. doi: 10.2217/nnm-2018-0302. Epub 2018 Dec 6.
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.
MATERIALS & METHODS: 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.
碳酸钙纳米颗粒（纳米 CaCO）可中和实体瘤的酸性 pH 值，但缺乏内在的成像信号，无法对肿瘤微环境中 pH 值的变化进行非侵入式监测。我们旨在开发一种纳米 CaCO 的治疗诊断版本，以非侵入性地监测 pH 值的调节及其后续的肿瘤反应。
我们合成了具有 CaCO 涂层的铁磁核（磁铁矿 CaCO）。磁共振成像（MRI）用于确定使用纤维肉瘤和乳腺癌模型的生物分布和 pH 值调节。
磁铁矿 CaCO-MRI 成像显示，纳米 CaCO 可迅速升高肿瘤 pH 值，随后在其清除后出现过度的肿瘤相关酸性产物。连续输注纳米 CaCO 可抑制转移。
纳米 CaCO 的暴露诱导了肿瘤的代谢重编程，这可能是先前间歇性 pH 值调节策略未能实现可持续治疗效果的原因。
