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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY · 2023 · IF 4.3

Fluorescence studies of double-emitting carbon dots and application in detection of H2O in ethanol and differentiation of cancer cell and normal cell

Hao Zou,Xiaokun Liao,Xingjian Lu,Xiaoyan Hu,Yue Xiong,Jun Cao,Jiaqi Pan,Chaorong Li,Yingying Zheng

Herein, phenylalanine-bound carbon dots (CDs) with dual fluorescence emission peak behavior were reported, one of which was excitation-dependent and the other was not. The amino and carboxyl groups on the surface of CDs had a certain influence on their fluorescence. When the amino and carboxyl groups on the surface of CDs were removed, their fluorescence was significantly   weakened. The prepared CDs had solvent effect, and the emission peak of CDs shifted according to the change of the polarity of the solvent. Based on this, a method was developed for detecting water content in ethanol using CDs as a ratio probe. The change in the ratio of the intensity of the two emission peaks corresponded to the change of water content in ethanol. The detection linearity was good. In addition, the resulting CDs had good biocompatibility and could be enormously transported into cancer cells by the amino acid transporter on the surface of cancer cells, while normal cells only had a small amount of CDs   through   endocytosis, which laid the base for the distinguishing cancer cells from normal cells. The unique fluorescence properties of the prepared CDs achieved their applications in both water detection and cell differentiation.

研究领域: 分析化学 · 生物医学
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SENSORS AND ACTUATORS B-CHEMICAL · 2021 · IF 7.46

Tracking lipid droplet dynamics for the discrimination of cancer cells by a solvatochromic fluorescent probe

Linlin Yang,Jianping Wang,Bianhua Liu,Guangmei Han,Hong Wang,Liang Yang,Jun Zhao,Ming-Yong Han,Zhongping Zhang

High lipid metabolism is one of the fundamental characteristics of cancer cells different from normal cells due to lots of energy needed for the fast proliferation of cancer cells. As an important organelle to supply cellular energy, however, the difference of lipid droplets (LDs) in their dynamic features between cancer cells and normal cells remains unclear. A key difficulty is to develop a specific fluorescence-tunable probe with high signal-to-noise for rapidly and accurately identifying cancer cells via tracking lipid droplets’ dynamics. Here, we report a solvatochromic fluorescent probe, dansyl-morpholine (DNS-M), with high LDs-specificity to achieve the effective discrimination of cancer cells from normal cells by visually profiling the feature difference of LDs dynamics. Probe DNS-M is synthesized easily by one-step reaction, and possesses a large Stokes shift ∼200 nm, excellent photostablity and LDs-targeted capability with high overlap coefficient up to 0.97. Due to the remarkable biomembrance penetration, LDs-specificity and photostability, DNS-M has been applied to distinguish cancer cells from normal cells rapidly within 1 min in living cells and fixed cells, and real-time track dynamic behaviors of LDs in cancer cells, such as association, dissociation and fusion. More importantly, a significant difference in LDs behavior modes between cancer cells and normal cells is successfully visualized for the first time with our probe. We envision that our probe will become a rapid and easy-to-operate tool for cancer diagnosis and deeper understanding of LDs-related behaviors in cancer cells.

CAS / MDL: 7385-67-3 112-80-1
研究领域: 生物化学 · 肿瘤学 · 细胞生物学
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 30 ·5796-5803 · IF 7.571

Distinguishing cancer cells from normal cells with an organelle-targeted fluorescent marker

Hao-Chi Hao,Gang Zhang,Ya-Nan Wang,Ru Sun,Yu-Jie Xu,Jian-Feng Ge

In this paper we report a hemicyanine dye that is used to distinguish cancer cells from normal cells with its ability to target different organelles. Probe 1, a red emission hemicyanine functional dye, was connected to oxazolo[4,5-b]pyridine and diethylaminobenzene with a double bond. The maximum absorption peaks of probe 1 were located in the 509–552 nm range in organic solvents. Meanwhile, the probe possessed a high molar extinction coefficient (5.50 × 104 M−1 cm−1 in DMSO) with high photostability. The maximum emission wavelength of the probe ranged from 572 nm to 644 nm, and it also had a large Stokes shift (126 nm in DMSO). In particular, the probe showed weak fluorescence in water (Φ = 0.016), whereas it displayed strong fluorescence at 595 nm in β-cyclodextrin (β-CD) solution (Φ = 0.13). In addition, cell colocalization experiments showed that probe 1 (3 μM) was located in the endoplasmic reticulum in cancer cells, while it could target lysosomes in normal cells. What's more, further cell imaging experiments demonstrated that the average fluorescence intensity of probe 1 (0.3 μM) in cancer cells increased with the addition of β-CD, but it did not occur in normal cells. The study provides a convenient way to distinguish cancer cells from normal ones, which has potential for application in the early detection of cancer.

研究领域: 生物化学 · 肿瘤学 · 医学成像
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Nanoscale · 2017 ·Vol. 9 ·期 46 ·18368-18378 · IF 7.367

Mitochondria-targetable carbon quantum dots for differentiating cancerous cells from normal cells

Ge Gao,Yao-Wen Jiang,Jingjing Yang,Fu-Gen Wu

In this study, a series of fluorescent carbon quantum dots (or carbon dots, CDs) with inherent mitochondrial targeting/imaging and cancerous/normal cell differentiation capabilities were prepared by a one-pot solvothermal treatment of glycerol and a silane molecule. Glycerol acted as a solvent and carbon source, and the silane molecule acted as a passivation agent. The as-prepared CDs could specifically and stably (for at least 24 h) visualize mitochondria of various types of cells without the introduction of mitochondria-targeting ligands (such as triphenylphosphonium). In addition, the CDs exhibited extraordinary features including facile synthesis, good water solubility, favorable biocompatibility, and excellent photostability as compared to commercial mitochondrial probes. Moreover, the CDs could efficiently distinguish cancerous cells from normal cells with high fluorescence contrast due to differences in their mitochondrial membrane potentials and substance uptake efficiencies. More importantly, to the best of our knowledge, the present study provides the first example of using CDs to distinguish cancerous cells from normal cells. The remarkable features of mitochondria-targeted imaging and cancerous cell recognition make the CDs an excellent fluorescent probe for various biomedical applications.

研究领域: 生物医学 · 材料科学 · 细胞生物学
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

A MOF-Shell-Confined I-Motif-Based pH Probe (MOFC-i) Strategy for Sensitive and Dynamic Imaging of Cell Surface pH

Huihui Yang,Jun Chen,Yuling Liang,Yanfei Zhang,Wen Yin,Yuzhi Xu,Si-Yang Liu,Zong Dai,Xiaoyong Zou

Dynamic imaging of cell surface pH is extremely challenging due to the slight changes in pH and the fast diffusion of secreted acid to the extracellular environment. In this work, we construct a novel metal–organic framework (MOF)-shell-confined i-motif-based pH probe (MOFC-i) strategy that enables sensitive and dynamic imaging of cell surface pH. The CY3- and CY5-labeled i-motif, which is hybridized via its short complementary chain with two-base mismatches, is optimized for sensing at physiological pH. After efficiently anchoring the optimized pH probes onto the cell membrane with the aid of cholesterol groups, a biocompatible microporous MOF shell is then formed around the cell by cross-linking ZIF-8 nanoparticles via tannic acid. The microporous MOF shell can confine secreted acid without inhibiting the normal physiological activities of cells; thus, the MOFC-i strategy can be used to monitor dynamic changes in the cell surface pH of living cells. Furthermore, this method can not only clearly distinguish the different metabolic behaviors of cancer cells and normal cells but also reveal drug effects on the cell surface pH or metabolism, providing promising prospects in pH-related diagnostics and drug screening.

研究领域: 生物化学 · 细胞生物学 · 分子生物学 · 生物医学工程
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BIOSENSORS & BIOELECTRONICS · 2021 · IF 10.618

Molecularly assembled graphdiyne with atomic sites for ultrafast and real-time detection of nitric oxide in cell assays

Xijuan Hao,Fangxin Hu,Yu Gu,Hongbin Yang,Changming Li,Chunxian Guo

Nitric oxide as a signal molecule participates in a variety of physiological and pathological processes but its real-time detection in cell assays still faces challenging because of the trace amount, short half-life and easy conversion to other substances. We report here a rational design by assembling highly π-conjugated and small capacitive gaphdiyne (GDY) with a coordination complex of hemin (HEM) into a molecularly assembled material of GDY/HEM to achieve ultrafast and real-time monitoring of nitric oxide in cell assays. GDY comprising alkynyl C atoms can hybridize with the HEM to enable strong π-π interaction and atomic dispersion of iron sites while avoiding the formation of catalytically inactive dimer for the HEM. These characteristics make the GDY/HEM an excellent sensing material towards nitric oxide, which has an ultrafast response time of 0.95 s, a low detection limit of 7 nM and long linear range up to 151.38 μΜ. The GDY/HEM realizes real-time monitoring nitric oxide released from cancer and normal cells, demonstrating its capability for cell analysis.

CAS / MDL: 16009-13-5
研究领域: 材料科学 · 分析化学 · 生物医学工程 · 细胞生物学
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ANALYTICAL CHEMISTRY · 2019 · IF 6.35

Living-Cell Imaging of Mitochondrial Membrane Potential Oscillation and Phenylalanine Metabolism Modulation during Periodic Electrostimulus

Guohua Qi,Bo Wang,Ying Zhang,Haijuan Li,Chuanping Li,Weiqing Xu,Yongdong Jin

Special electrosensory cells are sensitive to electric fields and give responses upon stimulation, but little is known about normal regular cells and cancerous cells. Herein, by designing nucleus- and mitochondria-targeting SERS nanoprobes combined with fluorescent monitoring of the mitochondrial membrane potential (MMP) variations, we found an interesting electrosensory and self-healing response in MMP within cancerous and normal cells during periodic impulse electrostimulation (IES). More importantly, the key regulator role of phenylalanine (phe) was revealed by cell fluorescent imaging and SERS detection, whose expression level was increased in response to IES to induce cell apoptosis. During IES off-state, the self-repair function of cells was activated to reduce phe release. We also found that cancerous cells (MCF-7 and HeLa cells) demonstrated a response more remarkable than that of normal cells (L929 and H8 cells) to periodic IES. Our finding revealed a common electrosensory and self-repair biofunction of cells and its related phe metabolism response. Understanding the difference of biophysical/electrophysiological responses between cancerous and normal cells may broaden the view for cancer therapy in the future.

研究领域: 生物物理学 · 电生理学 · 癌症生物学 · 细胞生物学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2022 · IF 4.831

Construction of continuously enhanced fluorescent sensor for detection of glutathione in normal and cancer cells

Erfei Dong,Ting Chen,Min Fang,Weiju Zhu,Cun Li

In this paper, water-soluble cysteamine (CA)-capping CdSe quantum dots (CA-CdSe) could be used as a continuous fluorescent sensor. The CA-CdSe QDs can respond to Ag + with a detection limit of 54.1 nM. Interestingly, CA-CdSe quantum dots combined with Ag + to generate a new nano-fluorescence sensor-Ag + modified CA-CdSe QDs (Ag + @CA-CdSe). Ag + @CA-CdSe can detect glutathione (GSH) with good sensitivity and anti-interference performance. The detection limit of Ag + @CA-CdSe fluorescenct sensor for GSH is as low as 0.74 μM. In addition, the novel nano-fluorescent sensor Ag + @CA-CdSe exhibited good cell permeability and was successfully applied to detect exogenous and endogenous GSH concentrations in cells. It could distinguish cancerous and normal cells by in vitro cell fluorescence imaging.

研究领域: 纳米技术 · 生物医学工程 · 分析化学 · 细胞生物学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Optical activity invertible chiral WSe2 quantum dots as intracellular redox state indicator and regulator

Haimei Yang,Zixuan Ding,Jiayin Du,Xianlin He,Jianan Huang

Indicating and regulating intracellular redox states is crucial in interrogating their dynamic biological processes in healthy and disease states. However, this goal is subjected to dynamic changes in cellular redox. Herein, an optical invertible chiral WSe 2 QDs (L-Cys-WSe 2 QDs) for indicating and regulating the dynamic changes of intracellular redox state was developed based on ligand exchange. The L-Cys-WSe 2 QDs could respond specifically to cellular GSH with excellent anti-interference capability and high stability. This chiral probe was also applied to discriminate normal and cancerous cells on the basal of their different GSH levels. The universal application in indicating the different redox states within cells was demonstrated as well. Moreover, the as-prepared chiral WSe 2 QDs displayed good glutathione peroxidase (GPx)-like activity to regulate intracellular redox state by catalytically reducing toxic H 2 O 2 in vitro and in vivo . We anticipate that the chiroptical invertible probe should have broad applications in the dynamic analysis of the redox-based process in vivo .

研究领域: 生物化学 · 纳米医学 · 细胞生物学
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JOURNAL OF MOLECULAR LIQUIDS · 2021 · IF 6.165

Self-assembled DNA nanotrains for targeted delivery of mithramycin dimers coordinated by different metal ions: Effect of binding affinity on drug loading, release and cytotoxicity

Danfeng Wang,Min Liu,Yushu Wu,Yanna Zhao,Qingpeng Wang,Tianxin Weng,Lu Wang,He Liu,Yongfang Ren,Jun Han

Self-assembled DNA nanostructures, as a novel type of nano-biomaterials, are widely used for smart and targeted drug delivery due to their precise structures and versatile functions. The binding affinity of drugs to DNA nanostructures plays an important role in drug loading, release and efficacy. The interaction of mithramycin (MTR) with AS1411-tethered DNA nanotrains (AS1411NTrs) in the presence of different divalent metal ions (Mg 2+ , Zn 2+ , and Mn 2+ ) was studied by fluorescence spectroscopy, differential scanning calorimetry and viscosity measurement. The binding mode between the MTR dimers and AS1411NTrs was determined by viscosity experiment and melting temperature measurement. The thermodynamic parameters of the binding process (binding stoichiometry, binding constant, enthalpy change, entropy change and Gibbs free energy change) were determined by fluorescence spectroscopy and differential scanning calorimetry, and the effect of different metal ions on the binding was compared. The release of the MTR dimers loaded by AS1411NTrs in the absence and presence of DNase I was analyzed. The in vitro cytotoxicity of the MTR dimers to HepG2 cancer cells and L02 normal cells and their intracellular uptake efficiency were evaluated. The binding parameters were correlated with the loading, release and cytotoxicity of the MTR dimers. These studies showed that AS1411NTrs had high drug loading and sustained release effect on (MTR) 2 Mg 2+ , (MTR) 2 Zn 2+ and (MTR) 2 Mn 2+ . This drug loading system improved the lethality to cancer cells and reduced the side effects on normal cells. This study may provide a theoretical basis for the clinical application of MTR loaded by DNA nanostructures.

研究领域: 纳米技术 · 药学 · 生物技术 · 癌症研究 · 分子生物学
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Nanoscale · 2023 · IF 6.7

Evaluation of exogenous therapeutic protein activity under confinement and crowding effects

Jie Dai,Zhiyi Peng,Shuwei Shen,Binbin Huang,Lili Ren,Jia Liu,Chia Hung Chen,Guoguang Chen

The dysfunction of intracellular proteins is frequently associated with various diseases, such as cancer. The exogenous proteins in cells are usually assembled with specific configurations due to physiological confinement/crowding to exhibit novel features in protein structure, folding or conformational stability, distinguished with their behaviors in buffer solutions. Here, we synthesized exogenous proteins in a confined/crowded condition, to explore protein activity within the cells. The findings suggested that the confinement and crowding effects on protein activity are heterogeneous; they showed an inhibitory consequence on HRP by decreasing Km (from ~9.5- and ~21.7-fold) and Vmax (from ~6.8- and ~20.2-fold) lower than that of dilute solutions. Interestingly, the consequences on Cyt C seem more complicated, and the crowding exerts a positive effect by increasing Km ~3.6-fold and Vmax ~1.5-fold higher than that of dilute solutions; however, the confinement takes a negative consequence by decreasing Km ~2.0 and Vmax ~8.3 times. Additionally, in contrast to traditional nanoparticles-based confinement models, we synthesized a biodegradable nanoparticle to mimic the confined space, and the biggest advantage of this novel model is that the particles can be degraded and thus it can provide more intuitive observations of the target protein properties under the confinement and after release. Furthermore, we also evaluated protein activity in different cellular environments, indicating the exogenous protein activity was closely related to the crowdedness of cellular environments, and the inhibition of protein activity in MDA-MB-231 cancer cells was more obvious than HEK293 normal cells. Finally, SAXS analysis revealed the correlation between the protein conformation and the different environments. Our work will provide a unique way for precisely assessing whether the target cellular environments are native matrix in which specific exogenous protein drugs delivered to function or whether they display a therapeutic role, which is of great significance for screening and development of new drugs.

CAS / MDL: 54827-17-7
研究领域: 生物物理学 · 细胞生物学 · 药学 · 纳米技术
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Small · 2024 · IF 13

Hollow CoFe Nanozymes Integrated with Oncolytic Peptides Designed via Machine-Learning for Tumor Therapy

Feiyu Li,Bocheng Xu,Zijie Lu,Jiafei Chen,Yike Fu,Jie Huang,Yizhen Wang,Xiang Li

Developing novel substances to synergize with nanozymes is a challenging yet indispensable task to enable the nanozyme-based therapeutics to tackle individual variations in tumor physicochemical properties. The advancement of machine learning (ML) has provided a useful tool to enhance the accuracy and efficiency in developing synergistic substances. In this study, ML models to mine low-cytotoxicity oncolytic peptides are applied. The filtering Pipeline is constructed using a traversal design and the Autogluon framework. Through the Pipeline, 37 novel peptides with high oncolytic activity against cancer cells and low cytotoxicity to normal cells are identified from a library of 25,740 sequences. Combining dataset testing with cytotoxicity experiments, an 80% accuracy rate is achieved, verifying the reliability of ML predictions. Peptide C2 is proven to possess membranolytic functions specifically for tumor cells as targeted by Pipeline. Then Peptide C2 with CoFe hollow hydroxide nanozyme (H-CF) to form the peptide/H-CF composite is integrated. The new composite exhibited acid-triggered membranolytic function and potent peroxidase-like (POD-like) activity, which induce ferroptosis to tumor cells and inhibits tumor growth. The study suggests that this novel ML-assisted design approach can offer an accurate and efficient paradigm for developing both oncolytic peptides and synergistic peptides for catalytic materials.

CAS / MDL: 78-10-4 34819-78-8
研究领域: 生物技术 · 癌症研究 · 纳米技术 · 机器学习 · 药学
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