bims-glucam 2025-05-11 papers

bims-glucam

Biomed News

on Glutamine cancer metabolism

Issue of 2025–05–11
twelve papers selected by
Sreeparna Banerjee, Middle East Technical University

The role of SLC7A11 in arsenite-induced oncogenic phenotypes of human bronchial epithelial cells: A metabolic perspective.
Inhibition of Glutathione Pathway by Oleanolic Acid via PSAT1 Leads to Ferroptosis in Colorectal Cancer.
Glutamine signaling specifically activates c-Myc and Mcl-1 to Facilitate cancer cell proliferation and survival.
Purpurin/Indocyanine Green Nanocomposite for Restricting Glutaminolysis to Enhance Dual Phototherapy of Cancer.
Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression.
Exploring cellular metabolic kinetics through spectroscopic analysis of extracellular environments.
Cellular metabolomics study in colorectal cancer cells and media following treatment with 5-fluorouracil by gas chromatography-tandem mass spectrometry.
Enzymes Drive Glutathione Shunt to Explain Oxidative State Using an In-Parallel Multi-Omic Method.
A patent review of IDH1 inhibitors (2018-present).
Glutaminolysis and α-ketoglutarate-stimulated KCa3.1 expression contribute to β-adrenoceptor activation-induced myocardial fibrosis in mice.
Removing Barriers to Tumor 'Oxygenation': Depleting Glutathione Nanozymes in Cancer Therapy.
Thioether-bridged carbon dots-dopamine quinone conjugate probe for glutathione sensing and discrimination between glioblastoma and normal cells.

Environ Pollut. 2025 May 05. pii: S0269-7491(25)00754-7. [Epub ahead of print]376 126381

The role of SLC7A11 in arsenite-induced oncogenic phenotypes of human bronchial epithelial cells: A metabolic perspective.

Xin Fang, Yihui Ruan, Xianhang Yin, Junyi Wang, Chen Chen, Yuxin Hu, Huihui Wang, Jingbo Pi, Yuanyuan Xu.

  Chronic arsenic exposure enhances the probability of lung cancer with the underlying mechanisms remain unknown. Glutamine-driven synthetic metabolism, including nucleotide synthesis, amino acid production, TCA cycle replenishment, glutathione synthesis, and lipid biosynthesis, is crucial for both cancer initiation and progression. This study demonstrated that chronic exposure to 0.1 μM arsenite for as long as 36 weeks induced malignant transformation in human bronchial epithelial cells (BEAS-2B). Metabolomics were used to systematically disclose metabolic characteristics in arsenic-transformed malignant (As-TM) cells. Significantly changed metabolites were enriched in alanine, aspartate and glutamate metabolism, arginine biosynthesis, glutamine and glutamate metabolism, glutathione metabolism, butanoate metabolism, TCA cycle, and arginine and proline metabolism. It is worth noting that glutamate located at the intersection of the enriched metabolism pathways. Glutamine deprivation attenuated the oncogenic phenotypes, including capacity of wound healing and proliferation, in As-TM cells. And the expression levels of mRNA and proteins associated with glutamine metabolism-related transporters and enzymes, including SLC7A11, GCLM, and GCLC, were significantly increased, with SLC7A11 exhibiting the most substantial increase. Moreover, arsenite transformation progressively elevated SLC7A11 mRNA and protein levels over time. The SLC7A11 inhibitor sulfasalazine remarkably attenuated arsenite-induced oncogenic phenotypes. Collectively, our data suggest that chronic arsenite exposure enhances glutamine metabolism through upregulation of SLC7A11, thereby promoting cell proliferation and malignant transformation. These results provide new insights for preventive and therapeutic strategies for lung cancer linked to arsenic exposure.

Keywords:  Arsenite; Glutamine metabolic reprogramming; Lung cancer; Oncogenic phenotypes; SLC7A11

DOI:  https://doi.org/10.1016/j.envpol.2025.126381
Drug Dev Res. 2025 May;86(3): e70097

Inhibition of Glutathione Pathway by Oleanolic Acid via PSAT1 Leads to Ferroptosis in Colorectal Cancer.

Qing Sun, Ruolin Sun, Bokun He, Hongjie Meng, Jie Jin, Juhui He.

  Phosphoserine aminotransferase 1 (PSAT1), a pivotal regulator of serine metabolism, is overexpressed in a variety of cancers, yet its role in colorectal cancer (CRC) remains to be elucidated. Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid, is suspected to have the potential to regulate ferroptosis, though this capability has not been confirmed. Utilizing bioinformatics tools, we conducted an analysis of PSAT1 expression in CRC, pathway enrichment, and its correlation with proteins pivotal to glutathione metabolism and the induction of ferroptosis. Expression levels of PSAT1 were validated by Quantitative Polymerase Chain Reaction (qPCR) and western blot analysis (WB). Cell Counting Kit-8 (CCK-8) was employed to measure the viability of CRC cells. Ferroptosis was assessed via flow cytometry, Fe2+ detection, malondialdehyde (MDA) levels, and WB. The metabolic pathway of glutathione was examined by analyzing the levels of reduced glutathione (GSH) and glutathione disulfide (GSSG), glutamate, glutamine, and α-ketoglutarate, and by assessing the expression of rate-limiting enzymes in glutamine metabolism. The interaction between OA and PSAT1 was predicted by molecular docking and validated with the cellular thermal shift assay (CETSA) -WB assay. The results showed that PSAT1 was found to be highly expressed in CRC and enriched in pathways associated with ferroptosis and glutathione metabolism, instrumental in preserving the vitality of CRC cells. PSAT1 knockdown increased cellular lipid reactive oxygen species (ROS) and MDA, and ferrous ion accumulation, while also inhibiting the expression of ferroptosis markers Solute carrier family 7, membrane 11 (SLC7A11) and Glutathione peroxidase 4 (GPX4). Overexpression of PSAT1 raised the levels of glutathione metabolic intermediates and the GSH ratio, inhibiting ferroptosis, and these effects were reversed by methionine sulfoximine. OA was identified through molecular docking and CETSA-WB to effectively dock with PSAT1 and target it to inhibit glutathione metabolism, enhancing lipid peroxidation and Fe2+ accumulation in CRC cells. In conclusion, OA, upon binding to PSAT1, curbs its expression, which in turn downregulates glutathione metabolism and enhances ferroptosis in CRC cells.

Keywords:  PSAT1; colorectal cancer; ferroptosis; glutathione metabolism; oleanolic acid

DOI:  https://doi.org/10.1002/ddr.70097
Protein Cell. 2025 May 04. pii: pwaf029. [Epub ahead of print]

Glutamine signaling specifically activates c-Myc and Mcl-1 to Facilitate cancer cell proliferation and survival.

Meng Wang, Fu-Shen Guo, Dai-Sen Hou, Hui-Lu Zhang, Xiang-Tian Chen, Yan-Xin Shen, Zi-Fan Guo, Zhi-Fang Zheng, Yu-Peng Hu, Pei-Zhun Du, Chen-Ji Wang, Yan Lin, Yi-Yuan Yuan, Shi-Min Zhao, Wei Xu.

  Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the seven substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase (QARS). Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.

Keywords:  FBW7; Mcl-1; QARS; c-Myc; glutamine; glutamylation

DOI:  https://doi.org/10.1093/procel/pwaf029
Mol Pharm. 2025 May 04.

Purpurin/Indocyanine Green Nanocomposite for Restricting Glutaminolysis to Enhance Dual Phototherapy of Cancer.

Sen Li, Shenyi Wang, Yanfei Cai, Dong Hua, Jian Jin, Hao Zhang, Zhaoqi Yang.

  Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising noninvasive cancer treatments owing to their precision and convenience. Indocyanine green (ICG), a dual-functional agent capable of generating both PDT and PTT effects under single-wavelength laser irradiation, is widely explored in oncology. However, ICG faces limitations such as poor bioavailability, rapid systemic clearance, and tumor microenvironment glutathione (GSH) overexpression, which scavenges reactive oxygen species (ROS) and diminishes therapeutic efficacy. To address this, we developed albumin-based nanoparticles (ICG&purpurin@BSA) co-encapsulating ICG and purpurin. Purpurin inhibits mitochondrial glutaminolysis, a metabolic pathway critical for GSH synthesis, thereby reducing GSH-mediated ROS depletion. Flow cytometry and Western blot analyses confirmed significant GSH downregulation. The nanocomposite demonstrated robust anticancer effects in vitro and in vivo, achieving near 90% tumor growth suppression within 12 days. The outcomes of this research demonstrate the benefits of combining biocompatible nanocomposites with glutamine pathway inhibitors and dual phototherapy agent ICG.

Keywords:  Albumin; Glutaminolysis; Indocyanine green; Purpurin

DOI:  https://doi.org/10.1021/acs.molpharmaceut.5c00001
Redox Biol. 2025 Apr 30. pii: S2213-2317(25)00166-1. [Epub ahead of print]83 103653

Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression.

Amanda M Sherwood, Basma A Yasseen, Janine M DeBlasi, Samantha Caldwell, Gina M DeNicola.

  Redox regulators are emerging as critical mediators of lung tumorigenesis. NRF2 and its negative regulator KEAP1 are commonly mutated in human lung cancers, leading to NRF2 accumulation and constitutive expression of NRF2 target genes, many of which are at the interface between antioxidant function and anabolic processes that support cellular proliferation. Nrf2 activation promotes lung tumor initiation and early progression in murine models of lung cancer, but which Nrf2 targets mediate these phenotypes is unknown. Nrf2 regulates two parallel antioxidant systems mediated by thioredoxin reductase 1 (TXNRD1) and glutathione reductase (GSR), which promote the reduction of protein antioxidant thioredoxin (TXN) and tripeptide antioxidant glutathione (GSH), respectively. We deleted TXNRD1 and GSR alone, or in combination, in lung tumors harboring mutations in KrasG12D and Nrf2D29H. We found that tumor initiation was promoted by expression of GSR, but not TXNRD1, regardless of Nrf2 status. In contrast, Nrf2D29H tumors, but not Nrf2WT, were dependent on TXNRD1 for tumor progression, while GSR was dispensable. Simultaneous deletion of GSR and TXNRD1 reduced initiation and progression independent of Nrf2 status, but surprisingly did not completely abrogate tumor formation. Thus, the thioredoxin and glutathione antioxidant systems play unique roles in tumor initiation and progression.

Keywords:  Glutathione (GSH); Glutathione reductase (GSR); Kelch-like ECH-Associated protein 1 (KEAP1); Non-small cell lung cancer (NSCLC); Nuclear factor erythroid 2-related factor 2 (NRF2); Reactive oxygen species (ROS); Thioredoxin (TXN); Thioredoxin reductase (TXNRD1)

DOI:  https://doi.org/10.1016/j.redox.2025.103653
Spectrochim Acta A Mol Biomol Spectrosc. 2025 May 01. pii: S1386-1425(25)00614-6. [Epub ahead of print]340 126308

Exploring cellular metabolic kinetics through spectroscopic analysis of extracellular environments.

Zohreh Mirveis, Nitin Patil, Hugh J Byrne.

  Studying the kinetics of metabolic pathways, such as glycolysis and glutaminolysis, is valuable due to their fundamental links to various diseases, including cancer. This study explores the potential of Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy for analysing low concentrations of metabolites in extracellular media. It also evaluates the use of the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) method to data mine the kinetic evolution of the spectroscopic signatures of the glycolysis metabolic pathway and to explore the impact of the presence of glutamine on it. By extracting samples at specific time intervals and drying them on the ATR crystal, ATR-FTIR could effectively measure individual metabolites of glucose, glutamine and lactate at low concentrations, providing clear spectra with strong correlations between peak absorbance and metabolite concentrations. In data mining, MCR-ALS successfully resolved two components, glucose and lactate, from time-series data of cellular glucose metabolism (glycolysis), showing approximately 28 % glucose consumption and 1 mM lactate production at a constant rate of 0.0016 min-1. However, when glutamine was introduced as a third component, the overlap of the peaks of glutamine and lactate limited the method's ability to deconvolute the data, highlighting constraints of MCR-ALS in complex mixtures.

Keywords:  ATR-FTIR spectroscopy; Glutaminolysis; Glycolysis; MCR-ALS data analysis; Metabolic pathways kinetics; Spectral data mining

DOI:  https://doi.org/10.1016/j.saa.2025.126308
Metabolomics. 2025 May 07. 21(3): 62

Cellular metabolomics study in colorectal cancer cells and media following treatment with 5-fluorouracil by gas chromatography-tandem mass spectrometry.

Songjin Oh, Hyun Bo Sim, Hyeongyeong Kim, Seul-Ki Mun, Moongi Ji, Byeongchan Choi, Doo-Young Kim, Jong-Jin Kim, Man-Jeong Paik.

   BACKGROUND: Metabolic reprogramming is a distinctive characteristic of colorectal cancer (CRC) which provides energy and nutrients for rapid proliferation. Although numerous studies have explored the rewired metabolism of CRC, the metabolic alterations occurring in CRC when the cell cycle is arrested by treatment with 5-fluorouracil (5-FU), an anticancer drug that arrests the S phase, remain unclear.
METHODS: A systematic profiling analysis was conducted as ethoxycarbonyl/methoxime/tert-butyldimethylsilyl derivatives using gas chromatography-tandem mass spectrometry in HT29 cells and media following 5-FU treatment in a concentration- and time-dependent manner.
RESULTS: In HT29 cells of 24 h after 5-FU treatment (3-100 μM) and 48 h after 5-FU treatment (1-10 μM), six amino acids, including valine, leucine, isoleucine, serine, glycine, and alanine and two organic acids, including pyruvic acid and lactic acid, were significantly increased compared to the DMSO-treated group. However, 48 h after 5-FU treatment (30-100 μM) in HT29 cells, the levels of these metabolites decreased along with an approximately 50% reduction in viability, an increase in the level of reactive oxygen species, induction of cycle arrest in the G1 phase, and the induction of apoptosis. On the other hand, the levels of fatty acids showed a continuous increase in HT29 cells 48 h after 5-FU treatment (1-100 μM). In the media, the decreased availabilities in the cellular uptake of nutrient metabolites, including valine, leucine, isoleucine, serine, and glutamine, were observed at 48 h after 5-FU treatment in a dose-dependent manner.
CONCLUSION: It is assumed that there is a possible shift in energy dependence from the tricarboxylic acid cycle to fatty acid metabolism. Thus, metabolic profiling analysis revealed altered energy metabolism in CRC cells following 5-FU treatment.

Keywords:  5-Fluorouracil; Colorectal cancer; HT29 cells; Mass spectrometry; Metabolite profiling analysis; Metabolomics

DOI:  https://doi.org/10.1007/s11306-025-02263-x
Int J Mol Sci. 2025 Apr 11. pii: 3632. [Epub ahead of print]26(8):

Enzymes Drive Glutathione Shunt to Explain Oxidative State Using an In-Parallel Multi-Omic Method.

Valerie C Wasinger, Sonia Bustamante, Nashwa Najib, Ashish Diwan, Tharusha Jayasena, Nahian S Chowdhury, Julia Beretov, Siobhan Schabrun.

  The glutathione shunt is one of the most important contributors to the cellular redox state, with implications across cancer, chronic diseases, diseases of ageing, and autoimmune diseases, including inflammatory bowel disease (IBD). Traditionally, the redox state is gauged by the ratio of the surrogate metabolites GSH and GSSG. However, this presents methodological challenges and offers a constrained illustration of metabolites without a systems-level understanding of redox dynamics, failing to elucidate variations across an entire biochemical network. Targeted proteomics can fill this void. Here, we describe an in-parallel metabolomic and proteomic targeted method to encompass measurements directly related to the shunt. Samples are simultaneously prepared to extract the substrate building blocks, cysteine, cystine, methionine, glutamic acid, and kynurenine; and the proteins, SLC7A11 (xCT), Glutamate Cysteine Ligase (GSH1), Glutathione Synthetase (GSH2), Glutathione Peroxidase (GPx), and Glutathione Reductase (GSHR) for targeted mass spectrometry. We demonstrate the method by targeted analysis of proteins in plasma, serum, nasal swab, and saliva and apply the multi-omic method to assess changes in the glutathione shunt in the serum of patients diagnosed with IBD. This allows for a broader narrative to establish context at which the glutathione shunt is operating.

Keywords:  GPx; GSH; GSSG; IBD; SLCA7A1; biomarker; glutathione shunt; liquid biopsy

DOI:  https://doi.org/10.3390/ijms26083632
Expert Opin Ther Pat. 2025 May 07. 1-28

A patent review of IDH1 inhibitors (2018-present).

Qing Liang, Fei Wen, Peilin Wang, Yitong Jiang, Yuting Geng, Xiaoming Zha.

   INTRODUCTION: isocitrate dehydrogenase 1 (IDH1), a key metabolic enzyme in the cytosol, catalyzes the oxidative decarboxylation of isocitrate to produce α-ketoglutarate (α-KG) and NADPH in the TCA cycle. Pan-cancer studies have demonstrated that IDH1 exhibits a higher mutation frequency and is implicated in a broader range of cancer types, indicating its potential as a promising anti-tumor target.
AREAS COVERED: We summarized patents from 2018 to the present that identify novel molecules, compounds, formulations, and methods for inhibiting mIDH1. The literature was retrieved from Web of Science and PubMed. Patent information was obtained via the State Intellectual Property Office's Patent Search and Analysis platform. Clinical data were sourced from the Cortellis Drug Discovery Intelligence database. The date of the most recent search was .
EXPERT OPINION: Due to multiple signaling pathway dysregulations and compensatory pathways in solid tumor, monotherapies targeting mutant IDH1 (mIDH1) often fail to achieve desired therapeutic outcomes. Consequently, the combination of mIDH1 inhibitors with other therapeutic agents can enhance the efficacy of antitumor treatments and mitigate the risk of drug resistance. Moreover, the development of novel dual or multiple inhibitors and functional molecules targeting mIDH1 May represent a more promising approach.

Keywords:  IDH1; Tumors; clinical drugs; inhibitors; metabolism; novel compounds

DOI:  https://doi.org/10.1080/13543776.2025.2500959
Sci China Life Sci. 2025 May 07.

Glutaminolysis and α-ketoglutarate-stimulated KCa3.1 expression contribute to β-adrenoceptor activation-induced myocardial fibrosis in mice.

Ru-Yue Bai, Lin-Hong Wu, Yan Wang, Chen Guo, Gang She, Zheng-Da Pang, Jing-Jing Li, Xin-Yi Zhao, Meng-Zhuan Han, Xia-Xia Hai, Yi-Yi Yang, Yi Zhang, Li-Mei Zhao, Lian-Ying Jiao, Xiao-Jun Du, Xiu-Ling Deng.

  Heart failure is associated with myocardial fibrosis, a pivotal histopathological feature arising from β-adrenergic receptor (β-AR) stimulation through sympathetic nervous system activation. Augmented glutaminolysis with increased bioavailability of α-ketoglutarate (α-KG) is suggested to contribute to fibrogenesis and changes in cellular gene expression. KCa3.1 is a calcium-activated potassium channel expressed in fibroblasts and has been implicated in mediating fibrosis, yet the putative interactions between glutaminolysis and KCa3.1 in β-AR-mediated cardiac fibrosis remain poorly understood. Here, we performed a series of in vitro and in vivo experiments to investigate how α-KG might influence the expression of KCa3.1 in the context of experimental myocardial fibrosis driven by β-AR activation. In cultured adult mouse cardiac fibroblasts, α-KG exposure resulted in the upregulation of KCa3.1 mRNA and protein levels that were commensurate with the dose and duration of exposure, and also led to increased KCa3.1 channel currents. Exposure to α-KG led to a significant decrease in levels of histone methylation (H3K27me3) within the KCa3.1 promoter, a decrease in the association of the transcription repressor REST from this site, as well as an enrichment of transcription activator AP-1 binding. The exacerbated fibrotic signaling induced by α-KG in cultured fibroblasts was suppressed by functional inhibition of KCa3.1 or by genetic knockdown of Kcnn4. Moreover, β-AR activation by isoproterenol significantly augmented glutaminolysis mediated by glutaminase 1 (GLS1) and significantly increased α-KG levels detected in the supernatant of cultured fibroblasts and cardiomyocytes. In addition, isoproterenol-induced KCa3.1 expression in fibroblasts was curtailed by treatment with the GLS1 inhibitor CB-839, or by GLS1 gene knockdown, or by treatment with the selective β2-AR antagonist, ICI118551. In mouse models of established cardiac fibrosis evoked by isoproterenol-stimulation or β2-AR overexpression, treatment with CB-839 for 4 weeks suppressed the phenotypic features of fibrosis, and this was associated with a decline in α-KG tissue content, a lack of histone demethylation at the KCa3.1 promoter, as well as suppression of KCa3.1 expression. Taken together, our study demonstrates for the first time that glutaminolysis contributes to β-AR activation-induced myocardial fibrosis via α-KG-stimulated KCa3.1 expression. We anticipate that treatments which target the β-AR/GLS1/α-KG/KCa3.1 signaling pathway might be effective for cardiac fibrosis.

Keywords:  KCa3.1 channels; cardiac fibrosis; glutaminolysis; α-ketoglutarate; β-adrenergic receptor

DOI:  https://doi.org/10.1007/s11427-024-2811-x
Int J Nanomedicine. 2025 ;20 5613-5643

Removing Barriers to Tumor 'Oxygenation': Depleting Glutathione Nanozymes in Cancer Therapy.

Ruilong Sun, Ruitang Liu, Yongzheng Tian, Yunfei Li, Bo Fan, Songkai Li.

  Nanozymes are nanomaterials capable of mimicking natural enzyme catalysis in the complex biological environment of the human body. Due to their good stability and strong catalytic properties, nanozymes are widely used in various fields of biomedicine. Among them, nanozymes that trigger intracellular reactive oxygen species (ROS) levels for cancer therapy have gained significant attention. However, the 'explosion' of ROS in tumor cells was prevented by the high levels of glutathione (GSH) in the tumor microenvironment (TME). GSH, a prominent endogenous antioxidant, increases the resistance of tumor cells to oxidative stress by scavenging ROS. Certain nanozymes can deplete intracellular GSH levels by mimicking GSH oxidase (GSHOx), GSH peroxidase (GPx) or by interfering with the reduction of oxidized glutathione (GSSG). On the one hand, elevated the level of intracellular ROS and induced lipid peroxidation reaction leading to ferroptosis. On the other hand, it creates favorable conditions for the treatment of tumors with photodynamic therapy (PDT), sonodynamic therapy (SDT), chemodynamical therapy (CDT) and targeted therapy. In this paper, we present a comprehensive analysis of GSH-depleting nanozymes reported in recent years, including classification, mechanism, responsiveness to TME and their roles in cancer therapy, and look forward to future applications and developments.

Keywords:  cancer therapy; enzyme mimetic; glutathione depletion; nanomaterials; nanozymes; oxygen-dependent therapy

DOI:  https://doi.org/10.2147/IJN.S515734
Talanta. 2025 Apr 30. pii: S0039-9140(25)00739-8. [Epub ahead of print]294 128249

Thioether-bridged carbon dots-dopamine quinone conjugate probe for glutathione sensing and discrimination between glioblastoma and normal cells.

Ningcheng Wei, Yi Xiao, Yang Jin, Liying Zhang, Panpan Chen, Shuhu Du.

  Sensitive and specific recognition and imaging of glioblastoma (GBM) cells are crucial for early diagnosis in GBM. Herein, a novel thioether-bridged fluorescence carbon dots (CDs@S for short)-dopamine quinone (DAQ) conjugate (termed as CDs@S-DAQ) probe with red emission was fabricated for sensitive sensing of glutathione (GSH) and selective fluorescence imaging of GBM cells. Due to the strong photo-induced electron transfer (PET) effect between DAQ (the acceptor) and CDs@S (the donor), the red fluorescence of CDs@S is significantly quenched. In the presence of GSH, on the one hand, GSH reduces the quinone structure to a hydroquinone structure via Michael addition reaction, which eliminates the PET effect between DAQ and CDs@S, resulting in the fluorescence restoring of CDs@S; on the other hand, it simultaneously induces the cleavage of the thioether bond linking DAQ and CDs, causing DAQ to detach from the CDs surface and reducing the PET effect, which leads to the fluorescence recovery of CDs. It has been demonstrated that the response of CDs@S-DAQ probe to GSH has a good linear relationship in the range from 0.5 to 10 mM, with an R2 value of 0.9978. Meanwhile, the as-fabricated CDs@S-DAQ probe has excellent stability, superior optical properties and low cytotoxicity. Based on these findings, the probe can be applied in live-cell fluorescence imaging, enabling discrimination between GBM cells and normal tissue cells according to their distinct GSH expression levels.

Keywords:  GSH-responsive fluorescent probe; Glioblastoma cells imaging; Red-emitting carbon dots; Surface functionalization; Thioether bond

DOI:  https://doi.org/10.1016/j.talanta.2025.128249