A new fluorescent probe with a large turn-on signal for imaging nitroreductase in tumor cells and tissues by two-photon microscopy

Liu, Zhan-Rong; Tang, Yonghe; Xu, An; Lin, Weiying

doi:10.1016/j.bios.2016.09.107

Cited by 70 publications

(23 citation statements)

References 56 publications

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“…In this case, β-Galactosidase (β-gal) enzyme is used as a biomarker to detect the ovarian cancer cells ( Figure 6 [27]). Similarly, two-photon microscopes are used for investigating the biological functions and disorders in tumor cells [28] and to image the neural tissues of the brain [29]. Some of the multiphoton-based microscopes presented in the literature are listed by Li et al in [25].…”

Section: Multiphoton Microscopymentioning

confidence: 99%

Endoscopic Optical Imaging Technologies and Devices for Medical Purposes: State of the Art

2020

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The growth and development of optical components and, in particular, the miniaturization of micro-electro-mechanical systems (MEMSs), has motivated and enabled researchers to design smaller and smaller endoscopes. The overarching goal of this work has been to image smaller previously inaccessible luminal organs in real time, at high resolution, in a minimally invasive manner that does not compromise the comfort of the subject, nor introduce additional risk. Thus, an initial diagnosis can be made, or a small precancerous lesion may be detected, in a small-diameter luminal organ that would not have otherwise been possible. Continuous advancement in the field has enabled a wide range of optical scanners. Different scanning techniques, working principles, and the applications of endoscopic scanners are summarized in this review.

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Section: Multiphoton Microscopymentioning

confidence: 99%

Endoscopic Optical Imaging Technologies and Devices for Medical Purposes: State of the Art

2020

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“…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%

“…Compared to the developed two-photon fluorescent probe, probe TP-NO 2 showed a large two-photon action cross section (δ) value of 126 GM at 840 nm ( Figure S15), good selectivity and sensitivity with a low detection limit of 26 ng/ml, high molar absorption coefficient, high yield as well as long fluorescence emission wavelength that can avoid autofluorescence from organisms (Table S1). [21][22][23][24][25] The detailed synthesized steps were shown in Scheme S1.…”

Section: Design and Synthesis Of Tp-nomentioning

confidence: 99%

“…[10] NTR is seen as an indicator of highly invasive diseases in various hypoxic tumors and NTR overexpression plays important roles in tumor invasion, progression and angiogenesis [11]. Further studies show that the hypoxic status of solid tumors is closely related to the process of tumor progression [12]. Therefore, NTR can be selected as a biomarker and the hypoxia degree of solid tumor can be assessed by evaluating the NTR level [13].…”

Section: Introductionmentioning

confidence: 99%

“…Comparing to traditional one-photon fluorescent probes, two-photon fluorescent probes can achieve higher spatial and temporal resolution, deeper tissue imaging depth and longer observation time [21,51,52]. However, there are fewer two-photon fluorescent probes for NTR detection available so far, and the developed twophoton fluorescent probes usually have short fluorescence emission [21][22][23][24][25]. Thus powerful two-photon fluorescent probes with longer fluorescence emission wavelength are required urgently for NTR detection in tumor.…”

Section: Introductionmentioning

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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Two‐Photon Small‐Molecule Fluorogenic Probes for Visualizing Endogenous Nitroreductase Activities from Tumor Tissues of a Cancer Patient

Wang

Ding

et al. 2022

Adv Healthcare Materials

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Nitroreductase (NTR), a common enzymatic biomarker of hypoxia, is widely used to evaluate tumor microenvironments. To date, numerous optical probes have been reported for NTRs detection. Approaches capable of concisely guiding the probe design of NTRs suitable for deep‐tissue imaging, however, are still lacking. As such, direct optical imaging of endogenous NTR activities from tumors derived from cancer patients is thus far not possible. Herein, aided by computational calculations, the authors have successfully developed a series of two‐photon (TP) small‐molecule fluorogenic probes capable of sensitively detecting general NTR activities from various biological samples; by optimizing the distance between the recognition moiety and the reactive site of NTRs from different sources, the authors have discovered and experimentally proven that X4 displays the best performance in both sensitivity and selectivity. Furthermore, X4 shows excellent TP excited fluorescence properties capable of directly monitoring/imaging endogenous NTR activities from live mammalian cells, growing zebrafish, and tumor‐bearing mice. Finally, with an outstanding TP tissue‐penetrating imaging property, X4 is used, for the first time, to successfully detect endogenous NTR activities from the liver lysates and cardia tissues of a cancer patient. The work may provide a universal strategy to design novel TP small‐molecule enzymatic probes in future clinical applications.

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A new fluorescent probe with a large turn-on signal for imaging nitroreductase in tumor cells and tissues by two-photon microscopy

Cited by 70 publications

References 56 publications

Endoscopic Optical Imaging Technologies and Devices for Medical Purposes: State of the Art

Endoscopic Optical Imaging Technologies and Devices for Medical Purposes: State of the Art

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

Two‐Photon Small‐Molecule Fluorogenic Probes for Visualizing Endogenous Nitroreductase Activities from Tumor Tissues of a Cancer Patient

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