An ultrasensitive fluorogenic probe for revealing the role of glutathione in chemotherapy resistance

Jiang, Yuejing; Cheng, Juan; Yang, Chong; Hu, Yongzhou; Li, Jia; Han, Yifeng; Zang, Yi; Li, Xin

doi:10.1039/c7sc03338a

Cited by 53 publications

(35 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…hy926 cells were observed to have a lower GSH level than HUV-EC-C cells. The two cell lines were also stained with a GSH specific fluorescent probe NA8 [ 25 ], and HUV-EC-C cells demonstrated a much higher intracellular fluorescence ( Figs. 5 C and D), further confirming the higher GSH levels.…”

Section: Resultsmentioning

confidence: 99%

Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system

Dong

et al. 2020

Journal of Pharmaceutical Analysis

Self Cite

View full text Add to dashboard Cite

Nitric oxide (NO) is a second messenger playing crucial roles in the signaling of a variety of cellular functions. Due to its pathophysiological significance, various NO modulators have been developed to explore NO pathways and some have been used as therapies. These modulators are often used directly to observe pharmacological effects in cell lines, but their actual effect on intracellular NO level is seldom analyzed. Herein, facilitated by a selective and sensitive fluorescence probe, we observed that some NO modulators displayed unexpected behaviors with both NO scavenger carboxy-PTIO and endothelial nitric oxide synthase (eNOS) inhibitor N(ω)-nitro- l -arginine methyl ester ( l -NAME) failing to decrease intracellular free NO level in EA. hy926 cells while NO donor diethylamine-NONOate (DEA·NONOate) and eNOS activator calcimycin (A23187) failing to increase free NO level in human umbilical vein endothelial cell line (HUV-EC-C), although the reagents were confirmed to work normally in the primary human umbilical vein endothelial cells (primary HUVECs) and RAW 264.7 macrophage cells. Further research suggested that these unusual behaviors might be attributed to the cellular microenvironments including both the NO synthase (NOS) level and the endogenous glutathione (GSH) level. Genetically manipulating eNOS level in both cells restores the expected response, while decreasing GSH level restores the ability of DEA·NONOate to increase NO level in HUV-EC-C. These results reveal that the cellular microenvironment has a profound impact on pharmacological effect. Our study suggests GSH as a reservoir for NO in live cells and highlights the value of chemical probes as valuable tools to reveal microenvironment-dependent pharmacological effects.

show abstract

Section: Resultsmentioning

confidence: 99%

Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system

Dong

et al. 2020

Journal of Pharmaceutical Analysis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Apart from the over-expressed ASGPr receptors on cell membranes, the high intracellular concentration of GSH is another feature for HepG2 cells. Therefore, amounts of work on HepG2 cell imaging have targeted GSH as the characteristic biomarker [40–41]. Strategies like reduction of disulfide [42–44] and Michael addition [45–47] have been utilized to design fluorescent sensors for detecting intracellular GSH or discriminative sensing of GSH with other common biothiols (e.g., Cys and Hcy) [45–46].…”

Section: Resultsmentioning

confidence: 99%

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

Chai

Han

Zang

et al. 2019

Beilstein J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

The development of photochromic fluorescence sensors with dynamic and multiple-signaling is beneficial to the improvement of biosensing/imaging precision. However, elaborate designs with complicated molecular structures are always required to integrate these functions into one molecule. By taking advantages of both redox-active/high loading features of two-dimensional (2D) manganese dioxide (MnO2) and dynamic fluorescence photoswitching of photochromic sensors, we here design a hybrid photochromic MnO2 glycosheet (Glyco-DTE@MnO 2) to achieve the photoswitchable imaging of intracellular glutathione (GSH). The photochromic glycosheet manifests significantly turn-on fluorescence and dynamic ON/OFF fluorescence signals in response to GSH, which makes it favorable for intracellular GSH double-check in targeted human hepatoma cell line (HepG2) through the recognition between β-D-galactoside and asialoglycoprotein receptor (ASGPr) on cell membranes. The dynamic fluorescence signals and excellent selectivity for detection and imaging of GSH ensure the precise determination of cell states, promoting its potential applications in future disease diagnosis and therapy.

show abstract

“…In the meantime, HCC cells also have an elevated glutathione (GSH) level to protect themselves under ROS cytotoxicity (Cheng S.B. et al, 2017;Jiang et al, 2017). Consequently, GSH-responsive become one of most popular redox-responsive precision delivery strategies because of the higher GSH level in intracellular matrix of HCC cells than that in extracellular matrix or intracellular matrix of normal Chen et al, 2010Chen et al, , 2019Gao B. et al, 2015;Lv et al, 2015;Wang Y. et al, 2016;Wang et al, 2017a,b; RGD Integrin SMMC-7721, HepG2, Huh7…”

Section: Internal Stimulimentioning

confidence: 99%

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

Tao

Wang

2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal solid cancers globally. To improve diagnosis sensitivities and treatment efficacies, the development of new theranostic nanoplatforms for efficient HCC management is urgently needed. In the past decade, mesoporous silica nanoparticles (MSNs) with tailored structure, large surface area, high agents loading volume, abundant chemistry functionality, acceptable biocompatibility have received more and more attention in HCC theranostic. This review outlines the recent advances in MSNs-based systems for HCC therapy and diagnosis. The multifunctional hybrid nanostructures that have both of therapy and diagnosis abilities are highlighted. And the precision delivery strategies of MSNs in HCC are also discussed. Final, we conclude with our personal perspectives on the future development and challenges of MSNs.

show abstract

An ultrasensitive fluorogenic probe for revealing the role of glutathione in chemotherapy resistance

Abstract: Unveiling the detailed roles of glutathione (GSH) in chemoresistance necessitates a reliable assay for its detection in intact live specimens.

Cited by 53 publications

References 34 publications

Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system

Selective and sensitive fluorescence imaging reveals microenvironment-dependent behavior of NO modulators in the endothelial system

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

Contact Info

Product

Resources

About