title: pH-Activatable MnO-Based Fluorescence and Magnetic Resonance Bimodal Nanoprobe for Cancer Imaging.
abstract: Stimuli-responsive nanoprobes that combine both fluorescence and magnetic resonance imaging (MRI) are anticipated to be highly beneficial for tumor visualization with high imaging sensitivity. By employing an interfacial templating scheme, a pH-activatable fluorescence/MRI dual-modality imaging nanoprobe is successfully developed based on the coencapsulation of MnO nanoparticles and coumarin-545T inside a hybrid silica nanoshell. To promote cancer cell targeting with high-specificity, the nanoprobes are also conjugated with folic acid to establish a greater affinity for cancer cells that over-express folate receptors on their cell membrane. In the new nanosystem, MnO nanoparticles are shown to function as an efficient fluorescence quencher of coumarin-545T prior to cellular uptake. However, fluorescence recovery is achieved upon acidic dissolution of the MnO nanoparticles following receptor-mediated endocytosis into the low pH compartments of the cancer cells. Meanwhile, the Mn(2+) ions thus released are also shown to exert a strong T1 contrast enhancement in the cancer cells. Therefore, by demonstrating the dual-activatable MRI and fluorescence imaging in response to the low pH conditions, it is envisioned that these nanoprobes would have tremendous potential for emerging cancer-imaging modalities such as image-guided cancer therapy.
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore.
authors.forename: Benedict You Wei
authors.initials: BY
authors.lastname: Hsu
authors.affiliation: Translational Molecular Imaging Group, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way, 02-02 Helios, Singapore, 138667, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Ng
authors.affiliation: UCL Medical School, University College London, London, UK.|Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, CA, 94304, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Tan
authors.affiliation: Centre for Advanced Biomedical Imaging, University College London, 72 Huntley Street, London, WC1E 6DD, UK.
authors.forename: John
authors.initials: J
authors.lastname: Connell
authors.affiliation: Centre for Advanced Biomedical Imaging, University College London, 72 Huntley Street, London, WC1E 6DD, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roberts
authors.affiliation: Centre for Advanced Biomedical Imaging, University College London, 72 Huntley Street, London, WC1E 6DD, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Lythgoe
authors.affiliation: Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, 08-03 Innovis, Singapore, 138634, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, 08-03 Innovis, Singapore, 138634, Singapore.
authors.forename: Siew Yee
authors.initials: SY
authors.lastname: Wong
authors.affiliation: Translational Molecular Imaging Group, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way, 02-02 Helios, Singapore, 138667, Singapore.
authors.forename: Kishore
authors.initials: K
authors.lastname: Bhakoo
authors.affiliation: Centre for Nanotechnology and Regenerative Medicine, UCL Division of Surgery and Interventional Science, University College London, Pond Street, London, NW3 2QG, UK.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
authors.affiliation: Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, 08-03 Innovis, Singapore, 138634, Singapore.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore, 117576, Singapore.
authors.forename: John
authors.initials: J
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010087:Oxides / Q000737:chemistry*; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D003287:Contrast Media; D003374:Coumarins; D017895:Manganese Compounds; D010087:Oxides; C027424:manganese oxide; D012822:Silicon Dioxide; C030123:coumarin
keywords: MRI; cancer imaging; coumarin; manganese oxide; pH-responsive