Integrating Fluorinated Polymer and Manganese-Layered Double Hydroxide Nanoparticles as pH-activated 19 F MRI Agents for Specific and Sensitive Detection of Breast Cancer

Cheng Zhang; Li Li; Felicity Y Han; Xinying Yu; Xiao Tan; Changkui Fu; Zhi Ping Xu; Andrew K Whittaker

doi:10.1002/smll.201902309

Integrating Fluorinated Polymer and Manganese-Layered Double Hydroxide Nanoparticles as pH-activated ¹⁹ F MRI Agents for Specific and Sensitive Detection of Breast Cancer

Small. 2019 Sep;15(36):e1902309. doi: 10.1002/smll.201902309. Epub 2019 Jul 22.

Authors

Cheng Zhang^{1

2

3}, Li Li¹, Felicity Y Han^{1

4}, Xinying Yu^{1

5}, Xiao Tan^{1

5}, Changkui Fu^{1

2}, Zhi Ping Xu¹, Andrew K Whittaker^{1

2}

Affiliations

¹ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia.
² ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, Queensland, 4072, Australia.
³ Materials Research Laboratory, University of California, Santa Barbara, CA, 93106, USA.
⁴ School of Biomedical Science, The University of Queensland, Brisbane, Queensland, 4072, Australia.
⁵ School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072, Australia.

PMID: 31328398
DOI: 10.1002/smll.201902309

Abstract

¹⁹ F magnetic resonance imaging (¹⁹ F MRI) agents capable of being activated upon interactions with cancer triggers are attracting increasing attention, although challenges still remain for precise and specific detection of cancer tissues. In this study, a novel hybrid ¹⁹ F MRI agent for pH-sensitive detection of breast cancer tissues is reported, a composite system designed by conjugating a perfluoropolyether onto the surface of manganese-incorporated layered double hydroxide (Mn-LDH@PFPE) nanoparticles. The ¹⁹ F NMR/MRI signals from aqueous solutions of Mn-LDH@PFPE nanoparticles are quenched at pH 7.4, but "turned on" following a reduction in pH to below 6.5. This is due to partial dissolution of Mn²⁺ from the Mn-LDH nanoparticles and subsequent reduction in the effect of paramagnetic relaxation. Significantly, in vivo experiments reveal that an intense ¹⁹ F MR signal can be detected only in the breast tumor tissue after intravenous injection of Mn-LDH@PFPE nanoparticles due to such a specific activation. Thus pH-activated Mn-LDH@PFPE nanoparticles are a potential "smart" ¹⁹ F MRI agent for precise and specific detection of cancer diseases.

Keywords: activated agents; breast cancer; contrast agents; fluorine magnetic resonance imaging; paramagnetic relaxation enhancement.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / diagnosis*
Breast Neoplasms / diagnostic imaging
Contrast Media / chemistry
Female
Fluorocarbon Polymers / chemistry*
Humans
Hydrogen-Ion Concentration
Magnetic Resonance Imaging / methods*
Manganese / chemistry*
Nanoparticles / chemistry*
Sensitivity and Specificity

Substances

Contrast Media
Fluorocarbon Polymers
Manganese