Near-infrared off-on fluorescence probe activated by NTR for in vivo hypoxia imaging

Zheng, Jinrong; Shen, Yuanzhi; Xu, Zhiqiang; Yuan, Zhenwei; He, Yuanyuan; Chen, Wei; Er, Murat; Yin, Jun; Chen, Haiyan

doi:10.1016/j.bios.2018.08.014

Cited by 91 publications

(51 citation statements)

References 50 publications

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“…2f and h. Dicoumarin was a well-known inhibitor for NTR. [4,48] Then we incubated cells with 100 μM dicoumarin to inhibit NTR for 2 h. As shown in Fig. 2b, cells showed extremely weak fluorescence signals after incubated with dicoumarin, which further confirmed the selectivity of TP-NO 2 for NTR.…”

Section: Ntr Detection In Hypoxia Cellsmentioning

confidence: 56%

“…For NTR detection, many one-photon fluorescent probes have been developed. [4,10,26,27] However, two-photon fluorescent probes are currently rare. Herein, we designed a two-photon fluorescent probe for NTR detection.…”

Section: Design and Synthesis Of Tp-nomentioning

confidence: 99%

“…Hypoxia can lead to structures, functions and diffusion conditions of tumors disturbed, and it plays significant roles in tumor invasion, metastasis and drug resistance [3]. Researchers report that hypoxia causes many tumor-associated genes overexpress, especially hypoxia inducible factors 1α (HIF-1α) and HIF-mediated genes [4,5,48]. Within the hypoxic tumor microenvironment, HIF-1α promotes angiogenesis, metabolic adaptation, and other key aspects of tumor progression, which results in deteriorating tumor hypoxic microenvironment and abnormal microvessels.…”

Section: Introductionmentioning

confidence: 99%

“…NTR is an endogenous enzyme and closely related to oxygen concentration. The results of cell experiments indicated that the hypoxia degree of tumor cells can be evaluated by NTR detection[4,30,48]. Since our probe TP-NO 2 had been used for NTR detection successfully under different O 2 concentrations, we attempted to evaluate the NTR concentration fluctuations during the process of tumor treatment.…”

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confidence: 99%

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Rational design of a nitroreductase-activatable two-photon fluorescent probe for hypoxia imaging in cell and in vivo

Wang

Zhang

Huang

et al. 2020

Sensors and Actuators B: Chemical

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Tumor resistance is a huge challenge for tumor treatment, which may lead to tumor treatment failure. Relieving tumor resistance and improving efficacy are long-term goals for tumor treatment. Nitroreductase (NTR) is an endogenous enzyme that highly expressed in hypoxia tumors. Herein, we develop a NTR-activatable fluorescent probe, TP-NO 2 , for NTR detection during tumor treatment. TP-NO 2 with simple synthesis steps and high yield can qualitatively and quantitatively detect NTR in a wide range (0−20 μg/mL) with a detection limit of 26 ng/ mL. The probe has been successfully applied for NTR detection in cells under simulated hypoxia conditions. Hyperbaric oxygen (HBO) can alleviate tumor hypoxia and reduce NTR concentration. We pre-evaluate the effect of tumor treatment by NTR imaging. And the results demonstrate that HBO-assistant chemotherapy can effectively treat tumor cells. We further apply TP-NO 2 for NTR detection in A549 and cis-dichlorodiamineplatinum(II) (DDP)-resistant A549 (A549/DDP) xenograft nude mice, and we choose NTR as an indicator to pre-evaluate the treatment efficacy of malignant tumors. With the adjuvant therapy of HBO, chemotherapeutic drugs gemcitabine and carboplatin can effectively treat A549 and A549/DDP xenograft. These applications provide us a novel perspective for NTR imaging.

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Section: Ntr Detection In Hypoxia Cellsmentioning

confidence: 56%

Section: Design and Synthesis Of Tp-nomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Rational design of a nitroreductase-activatable two-photon fluorescent probe for hypoxia imaging in cell and in vivo

Wang

Zhang

Huang

et al. 2020

Sensors and Actuators B: Chemical

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“…1a). For instance, a recognition moiety (R) is modified to the D end to block its electron supply ("off"), before a specific analyte takes off (or changes) R to reactivate the D-to-A electron supply and emit fluorescence ("on") [20][21][22][23][24][25] . The status of the A end, or the influence of its change on fluorescence, is less noted.…”

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confidence: 99%

A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo

Xing

Niu

et al. 2020

Nat Commun

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Near-infrared (NIR) fluorescent probes are among the most attractive chemical tools for biomedical imaging. However, their in vivo applications are hindered by albumin binding, generating unspecific fluorescence that masks the specific signal from the analyte. Here, combining experimental and docking methods, we elucidate that the reason for this problem is an acceptor (A) group-mediated capture of the dyes into hydrophobic pockets of albumin. This pocket-capturing phenomenon commonly applies to dyes designed under the twisted intramolecular charge-transfer (TICT) principle and, therefore, represents a generic but previously unidentified backdoor problem. Accordingly, we create a new A group that avoids being trapped into the albumin pockets (pocket-escaping) and thereby construct a NIR probe, BNLBN, which effectively prevents this backdoor problem with increased imaging accuracy for liver fibrosis in vivo. Overall, our study explains and overcomes a fundamental problem for the in vivo application of a broad class of bioimaging tools.

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NIR‐II Cyanine Nanoparticles for Imaging‐Guided Tumor Targeting Photothermal Therapy with Vitamin C Enhanced Efficacy

Huang

Jiang

et al. 2023

Advanced Therapeutics

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Cyanine dyes in the near‐infrared‐II (NIR‐II) region are among the most promising photothermal agents, due to their high photothermal conversion efficiency, strong tumor targeting capability, and deep tissue penetration. The application of cyanine‐based photothermal agents remains limited, however, due to the invasive nature and spread of tumors as well as the potential for inflammatory responses during the treatment process. In this work, a naphtho[cd]indolium‐based heptamethine cyanine with NIR‐II emission is utilized to prepare PEGylated nanoparticles for studies of photothermal treatment. The results demonstrate that the nanoparticles have excellent NIR‐II imaging and tumor targeting capabilities. As a result of the light harvesting property of naphtho[cd]indolium‐based heptamethine cyanine, these nanoparticles demonstrate a photothermal conversion efficiency of 61%. The tumor‐targeting properties of these nanoparticles enable them to accumulate effectively at limbs containing tumors. Photothermal therapy shows almost complete disappearance of all tumors after eight days of treatment. In addition, hematoxylin‐eosin stains (H&E stains) of major organs show no discernible lesions throughout the treatment process. Furthermore, simultaneous injection of natural vitamin C during the treatment significantly improves the therapeutic effect of photothermal therapy.

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Near-infrared off-on fluorescence probe activated by NTR for in vivo hypoxia imaging

Cited by 91 publications

References 50 publications

Rational design of a nitroreductase-activatable two-photon fluorescent probe for hypoxia imaging in cell and in vivo

Rational design of a nitroreductase-activatable two-photon fluorescent probe for hypoxia imaging in cell and in vivo

A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo

NIR‐II Cyanine Nanoparticles for Imaging‐Guided Tumor Targeting Photothermal Therapy with Vitamin C Enhanced Efficacy

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