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Glutathione-Priming Nanoreactors Enable Fluorophore Core/Shell Transition for Precision Cancer Imaging
journal contribution
posted on 2019-08-23, 19:13 authored by Zhiqiang Lin, Changrong Wang, Yang Li, Ridong Li, Lidong Gong, Yue Su, Zheng Zhai, Xinyu Bai, Shiming Di, Zhao Li, Anjie Dong, Qiang Zhang, Yuxin YinIn
an attempt to develop an imaging probe with ultra-high sensitivity
for a broad range of tumors in vivo and inspired by the concept of
chemical synthetic nanoreactors, we designed a type of glutathione-priming
fluorescent nanoreactor (GPN) with an albumin-coating shell and hydrophobic
polymer core containing disulfide bonds, protonatable blocks, and
indocyanine green (ICG), a near-infrared fluorophore. The albumin
played multiple roles including biocompatible carriers, hydrophilic
stabilizer, “receptor” of the fluorophores, and even
targeting molecules. The protonation of the hydrophobic core triggered
the outside-to-core transport of acidic glutathione (GSH), as well
as the core-to-shell transference of ICGs after the disulfide bond
cleavage by GSH, which induced strong binding of fluorophores with
albumins on the GPN shell, initiating intensive fluorescence signals.
As a result, the GPNs demonstrated extremely high response sensitivity
and imaging contrast, proper time window, and broad cancer specificity.
In fact, an orthogonal activation pattern was found in vitro with
an ON/OFF ratio up to 24.7-fold. Furthermore, the nanoprobes specifically
amplified the tumor signals in five cancer-bearing mouse models and
actualized tumor margin delineation with a contrast up to 20-fold,
demonstrating much better imaging efficacy than the other four commercially
available probes. Therefore, the GPNs provide a new paradigm in developing
high-performance bioresponsive nanoprobes.
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GSHtumor signalsimaging probecancer specificityalbumin-coating shellimaging efficacydisulfide bond cleavageultra-high sensitivityorthogonal activation patternbiocompatible carriersICGfluorescence signalsdisulfide bondstime windowcancer-bearing mouse modelsactualized tumor margin delineationoutside-to-core transportacidic glutathionepolymer coreprotonatable blocksPrecision Cancer Imagingbioresponsive nanoprobesGPN shellnear-infrared fluorophorenanoreactorcore-to-shell transferenceimaging contrastresponse sensitivity
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