A novel CEST-contrast nanoagent for differentiating the malignant degree in breast cancer

Different subtypes of breast cancer (BCC) have variable degrees of malignancy, which is closely related to their extracellular pH (pHe). Therefore, it is increasingly significant to monitor the extracellular pH sensitively to further determine the malignancy of different subtypes of BCC. Here, a l-arginine and Eu3+ assembled nanoparticle Eu3+@l-Arg was prepared to detect the pHe of two breast cancer models (TUBO is non-invasive and 4T1 is malignant) using a clinical chemical exchange saturation shift imaging technique. The experiments in vivo showed that Eu3+@l-Arg nanomaterials could respond sensitively to changes of pHe. In 4T1 models, the CEST signal enhanced about 5.42 times after Eu3+@l-Arg nanomaterials were used to detect the pHe. In contrast, few enhancements of the CEST signal were seen in the TUBO models. This significant difference had led to new ideas for identifying subtypes of BCC with different degrees of malignancy.

[1]  Jian Wu,et al.  Blocking Spatiotemporal Crosstalk between Subcellular Organelles for Enhancing Anticancer Therapy with Nanointercepters , 2023, Advanced materials.

[2]  K. Hong,et al.  Hypoxia-Responsive Luminescent CEST MRI Agent for In Vitro and In Vivo Tumor Detection and Imaging. , 2022, Journal of medicinal chemistry.

[3]  Liangguo Zhang,et al.  Manganese-Based Multifunctional Nanoplatform for Dual-modal Imaging and Synergistic Therapy of Breast Cancer , 2022, Acta Biomaterialia.

[4]  Xiaoying Tang,et al.  A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging , 2021, International journal of molecular sciences.

[5]  M. Hadamitzky,et al.  Glioma: molecular signature and crossroads with tumor microenvironment , 2021, Cancer and Metastasis Reviews.

[6]  E. Rutgers,et al.  Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021 , 2021, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  J. Guan,et al.  Heterogeneity Within Molecular Subtypes of Breast Cancer. , 2021, American journal of physiology. Cell physiology.

[8]  J. Ferlay,et al.  Cancer statistics for the year 2020: An overview , 2021, International journal of cancer.

[9]  W. Bu,et al.  Intracellular Mutual Promotion of Redox Homeostasis Regulation and Iron Metabolism Disruption for Enduring Chemodynamic Therapy , 2021, Advanced Functional Materials.

[10]  P. Porporato,et al.  Tumour acidosis evaluated in vivo by MRI-CEST pH imaging reveals breast cancer metastatic potential , 2020, British journal of cancer.

[11]  Xin Hu,et al.  Metabolic-Pathway-Based Subtyping of Triple-Negative Breast Cancer Reveals Potential Therapeutic Targets. , 2020, Cell metabolism.

[12]  Jun Fang,et al.  Exploiting the dynamics of the EPR effect and strategies to improve the therapeutic effects of nanomedicines by using EPR effect enhancers. , 2020, Advanced drug delivery reviews.

[13]  Dario Livio Longo,et al.  Non-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging , 2020, Frontiers in Oncology.

[14]  Xiangming Fang,et al.  Negative CT Contrast Agents for the Diagnosis of Malignant Osteosarcoma , 2019, Advanced science.

[15]  R. Flavell,et al.  Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance , 2019, Cancers.

[16]  F. Arena,et al.  Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH , 2019, Cancer and Metastasis Reviews.

[17]  Samantha K. Barrick,et al.  Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions , 2018, Nature Communications.

[18]  Mark D. Pagel,et al.  Clinical applications of chemical exchange saturation transfer (CEST) MRI , 2018, Journal of magnetic resonance imaging : JMRI.

[19]  Jiadi Xu,et al.  Magnetization Transfer Contrast and Chemical Exchange Saturation Transfer MRI. Features and analysis of the field-dependent saturation spectrum , 2017, NeuroImage.

[20]  A. Sherry,et al.  Lanthanide-Based T2ex and CEST Complexes Provide Insights into the Design of pH Sensitive MRI Agents. , 2017, Angewandte Chemie.

[21]  É. Tóth,et al.  Lanthanide Complexes in Molecular Magnetic Resonance Imaging and Theranostics , 2017, ChemMedChem.

[22]  Robert J. Gillies,et al.  pH sensing and regulation in cancer , 2013, Front. Physiol..

[23]  H. Maeda,et al.  The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. , 2013, Advanced drug delivery reviews.

[24]  A. Sherry,et al.  Europium(III) DOTA-tetraamide complexes as redox-active MRI sensors. , 2012, Journal of the American Chemical Society.

[25]  A. Bradley,et al.  Imaging features, follow-up, and management of incidentally detected renal lesions. , 2011, Clinical radiology.

[26]  Ahmedin Jemal,et al.  Breast cancer statistics, 2011 , 2011, CA: a cancer journal for clinicians.

[27]  R. Gelber,et al.  Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011 , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  Nirbhay N. Yadav,et al.  Chemical exchange saturation transfer (CEST): What is in a name and what isn't? , 2011, Magnetic resonance in medicine.

[29]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[30]  R. Lenkinski,et al.  CEST and PARACEST MR contrast agents , 2010, Acta radiologica.

[31]  J. Srivastava,et al.  Structural model and functional significance of pH-dependent talin–actin binding for focal adhesion remodeling , 2008, Proceedings of the National Academy of Sciences.

[32]  A. Sherry,et al.  Modulation of water exchange in europium(III) DOTA-tetraamide complexes via electronic substituent effects. , 2008, Journal of the American Chemical Society.

[33]  C. Supuran,et al.  Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype , 2007, British Journal of Cancer.

[34]  Janet R Morrow,et al.  Europium(III) macrocyclic complexes with alcohol pendant groups as chemical exchange saturation transfer agents. , 2006, Journal of the American Chemical Society.

[35]  Robert E Lenkinski,et al.  PARACEST agents: modulating MRI contrast via water proton exchange. , 2003, Accounts of chemical research.

[36]  Jinyuan Zhou,et al.  Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI , 2003, Nature Medicine.

[37]  Susumu Mori,et al.  Mechanism of magnetization transfer during on‐resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids , 2003, Magnetic resonance in medicine.

[38]  D. Barber,et al.  Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1 , 2002, The Journal of cell biology.

[39]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Gottfried Otting,et al.  Proton exchange rates from amino acid side chains— implications for image contrast , 1996, Magnetic resonance in medicine.

[41]  R. Bryant,et al.  The dynamics of water-protein interactions. , 1996, Annual review of biophysics and biomolecular structure.

[42]  D. Page Prognosis and Breast Cancer: Recognition of Lethal and Favorable Prognostic Types , 1991, The American journal of surgical pathology.

[43]  R. Balaban,et al.  Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo , 1989, Magnetic resonance in medicine.