A Novel Fluorescent Probe Strategy Activated by β-Glucuronidase for Assisting Surgical Resection of Liver Cancer

Wang, Jiemin; Zhang, Liang; Su, Yaling; Qu, Yi; Cao, Yuping; Liu, Yun

doi:10.1021/acs.analchem.1c05635

Cited by 18 publications

(6 citation statements)

References 40 publications

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“…Moreover, owing to the superior ability to distinguish metastatic lesions, even those as small as 1 mm in diameter, image-guided resection, and imaging of metastatic cancer were successfully achieved by spraying YH-APN. Recently, Wang et al [ 212 ] also used an in situ spraying method that enabled precise distinguishing of the tumor edge under the guidance of fluorescent probes. During surgery, the use of real-time fluorescent imaging to detect β-glucuronidase (GLU) activity was achieved by DCDNO 2 , and the outlines of the tumor were visualized, which guided precise resection of liver cancer.…”

Section: Application Of Nanotechnology In Conquering Therapeutic Resi...mentioning

confidence: 99%

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Ren¹,

Zhang²,

Guo³

et al. 2023

World J Gastroenterol

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Colorectal cancer (CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance of CRC cells to different therapies, which can be summarized into two aspects: (1) The intrinsic characters and adapted alterations of CRC cells before and during treatment that regulate the drug metabolism, drug transport, drug target, and the activation of signaling pathways; and (2) the suppressive features of the tumor microenvironment (TME). To combat the issue of therapeutic resistance, effective strategies are warranted with a focus on the restoration of CRC cells’ sensitivity to specific treatments as well as reprogramming impressive TME into stimulatory conditions. To date, nanotechnology seems promising with scope for improvement of drug mobility, treatment efficacy, and reduction of systemic toxicity. The instinctive advantages offered by nanomaterials enable the diversity of loading cargoes to increase drug concentration and targeting specificity, as well as offer a platform for trying the combination of different treatments to eventually prevent tumor recurrence, metastasis, and reversion of therapy resistance. The present review intends to summarize the known mechanisms of CRC resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapy, as well as the process of metastasis. We have also emphasized the recent application of nanomaterials in combating therapeutic resistance and preventing metastasis either by combining with other treatment approaches or alone. In summary, nanomedicine is an emerging technology with potential for CRC treatment; hence, efforts should be devoted to targeting cancer cells for the restoration of therapeutic sensitivity as well as reprogramming the TME. It is believed that the combined strategy will be beneficial to achieve synergistic outcomes contributing to control and management of CRC in the future.

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Section: Application Of Nanotechnology In Conquering Therapeutic Resi...mentioning

confidence: 99%

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Ren¹,

Zhang²,

Guo³

et al. 2023

World J Gastroenterol

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“…Surgical resection is one of the most common and effective techniques for treating malignancies. − Tumor recurrence commonly results from tumor-positive surgical margins and metastatic lesions. The complete removal of tumor-positive margins determines the outcome of the operation during the surgical procedure. − To provide real-time intraoperative assistance, some traditional imaging modalities such as intraoperative magnetic resonance imaging (MRI), − X-ray computed tomography (CT), − and intraoperative ultrasound (US) − have shown promise for tumor detection.…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Contrast of Tumor Imaging for Image-Guided Surgery Using a Tumor-Targeting Probiotic with the Continuous Expression of a Biomarker

Meng

Fan

et al. 2022

Anal. Chem.

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Tumor recurrence commonly results from tumor-positive resection margins and metastatic lesions. The complete removal of tumor-positive margins is particularly essential in clinics. Thus, we designed a strategy based on Escherichia coli Nissle 1917 (EcN) nitroreductase (NTR) with a polyethylene glycol (PEG) polymer coating (PC-EcN-NTR) to specifically target and colonize in tumors for high-contrast tumor imaging by providing a large amount of NTR as biomarkers in situ. NTR is a favorable biomarker for tumor detection and imaging. The nfsB-encoding plasmid with a 16S promoter was transfected into EcN for the continuous and stable expression of NTR (E. coli. NfsB). PC-EcN-NTR can accumulate and proliferate for a long time in tumors to substantially express NTR. When the NTR-activated fluorescence (FL) probe was sprayed on the tumor, the tumor region showed fluorescence signals within 5 min. Compared to the tumor without colonization with bacteria, the PC-EcN-NTR-colonized tumors displayed 3.15× enhanced fluorescence signals. Furthermore, the fluorescence signals of the whole tumor can last at least 3 h, which is suitable for a long and meticulous surgical operation. More importantly, in the PC-EcN-NTR-harboring tumor, obvious FL appeared even at the very edge (approximately 200 μm away from the edge) of the tumor tissue. A TCF-Based near-infrared-II fluorescent probe (probe 2) was designed and synthesized. Results similar to those of probe 1 were observed when probe 2 was used for in vivo tumor imaging, which further proved the generality of the enhancing ability of the tumor-targeting probiotic. This strategy will hopefully guide the surgical resection of tumors via monitoring intense NTR activity. It may spur the use of tumor-targeting probiotic and enzyme-activated fluorescent probes for the processes of tumor diagnosis and image-guided surgery.

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“…The shortage of β-glucuronidase in body tissues consequently results in proliferation of GAGs inside the lysosomes, leading to the enlargement of their size . As a consequence of over-expression of this enzyme in various cancers like the neoplasm of bladder, liver cancer, and colon carcinoma, , the quantitative measurement of β-glucuronidase has been proved as a detection tool at the initial stage diagnosis of cancer and the assessment of therapeutic treatments. , Moreover, it is evident from the literature that an elevated level of β-glucuronidase in blood serum is related to various physiological disorders such as urinary tract infection, rejection of transplantation, epilepsy, renal diseases, rheumatoid arthritis, and larynx and breast cancer . Besides these, acquired immune deficiency syndrome (AIDs) and hepatic disorders have also been reported as a consequence of a high level of this enzyme. , …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation, and In Silico Studies of Novel Coumarin-Based 4H,5H-pyrano[3,2-c]chromenes as Potent β-Glucuronidase and Carbonic Anhydrase Inhibitors

et al. 2022

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The search for novel heterocyclic compounds with a natural product skeleton as potent enzyme inhibitors against clinical hits is our prime concern in this study. Here, a simple and facile two-step strategy has been designed to synthesize a series of novel coumarin-based dihydropyranochromenes ( 12a – 12m ) in a basic moiety. The synthesized compounds were thus characterized through spectroscopic techniques and screened for inhibition potency against the cytosolic hCA II isoform and β-glucuronidase. Few of these compounds were potent inhibitors of hCA II and β-glucuronidase with varying IC 50 values ranging from 4.55 ± 0.22 to 21.77 ± 3.32 μM and 440.1 ± 1.17 to 971.3 ± 0.05 μM, respectively. Among the stream of synthesized compounds, 12e and 12i were the most potent inhibitors of β-glucuronidase, while 12h , 12i , and 12j showed greater potency against hCA II. In silico docking studies illustrated the significance of substituted groups on the pyranochromene skeleton and binding pattern of these highly potent compounds inside enzyme pockets.

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A Novel Fluorescent Probe Strategy Activated by β-Glucuronidase for Assisting Surgical Resection of Liver Cancer

Cited by 18 publications

References 40 publications

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Enhancing the Contrast of Tumor Imaging for Image-Guided Surgery Using a Tumor-Targeting Probiotic with the Continuous Expression of a Biomarker

Synthesis, Biological Evaluation, and In Silico Studies of Novel Coumarin-Based 4H,5H-pyrano[3,2-c]chromenes as Potent β-Glucuronidase and Carbonic Anhydrase Inhibitors

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