TY - JOUR
T1 - Distinct ON/OFF fluorescence signals from dual-responsive activatable nanoprobes allows detection of inflammation with improved contrast
AU - Viger, Mathieu L.
AU - Collet, Guillaume
AU - Lux, Jacques
AU - Nguyen Huu, Viet Anh
AU - Guma, Monica
AU - Foucault-Collet, Alexandra
AU - Olejniczak, Jason
AU - Joshi-Barr, Shivanjali
AU - Firestein, Gary S.
AU - Almutairi, Adah
N1 - Funding Information:
This research was made possible by an NIH New Innovator Award (DP 2OD006499), King Abdulaziz City for Science and Technology (through the KACST-UCSD Center of Excellence in Nanomedicine and Engineering), National Institute of Arthritis and Musculoskeletal and Skin Diseases (MG: 1K08AR064834), NCRR (S10 RR027970), and NIH/NHLBI (P01 HL091830). NMR data was acquired at the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences NMR Facility. Serum biochemistry was undertaken and analyzed by the UCSD Animal Care Program Diagnostic Services Laboratory. Histological services were performed by the Moores Cancer Center Histology Core. Fluorescence imaging of the histological sections were performed at the UCSD School of Medicine Microscopy Core (NCI Support Grant P30 2P30CA023100-28). Animal imaging was done at the UCSD Animal Care Program Phenotyping Core. Usage of the IVIS® Spectrum permitted by Ellen C. Breen. The authors would like to express their gratitude to Arnold Garcia for his help with the animal experiments, to Minnie Chan and Sophia Suarez for their help with 1H NMR, to Ken Osborne for his help with interpretation of the serum biochemistry data, to Nissi Varki for her help with histopathology analysis and to Beatrix Bartok for her valuable input.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Visualization of biochemical changes associated with disease is of great clinical significance, as it should allow earlier, more accurate diagnosis than structural imaging, facilitating timely clinical intervention. Herein, we report combining stimuli-responsive polymers and near-infrared fluorescent dyes (emission max: 790 nm) to create robust activatable fluorescent nanoprobes capable of simultaneously detecting acidosis and oxidative stress associated with inflammatory microenvironments. The spectrally-resolved mechanism of fluorescence activation allows removal of unwanted background signal (up to 20-fold reduction) and isolation of a pure activated signal, which enables sensitive and unambiguous localization of inflamed areas; target-to-background ratios reach 22 as early as 3 h post-injection. This new detection platform could have significant clinical impact in early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection.
AB - Visualization of biochemical changes associated with disease is of great clinical significance, as it should allow earlier, more accurate diagnosis than structural imaging, facilitating timely clinical intervention. Herein, we report combining stimuli-responsive polymers and near-infrared fluorescent dyes (emission max: 790 nm) to create robust activatable fluorescent nanoprobes capable of simultaneously detecting acidosis and oxidative stress associated with inflammatory microenvironments. The spectrally-resolved mechanism of fluorescence activation allows removal of unwanted background signal (up to 20-fold reduction) and isolation of a pure activated signal, which enables sensitive and unambiguous localization of inflamed areas; target-to-background ratios reach 22 as early as 3 h post-injection. This new detection platform could have significant clinical impact in early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection.
KW - Inflammatory microenvironments
KW - Molecular imaging
KW - NIR optical nanoprobes
KW - Spectrally-resolved imaging
KW - Stimuli-responsive polymers
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U2 - 10.1016/j.biomaterials.2017.03.042
DO - 10.1016/j.biomaterials.2017.03.042
M3 - Article
C2 - 28433935
AN - SCOPUS:85018472989
SN - 0142-9612
VL - 133
SP - 119
EP - 131
JO - Biomaterials
JF - Biomaterials
ER -