ACS Applied Materials & Interfaces
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2021
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IF 9.229
Juanfeng Ou,Hao Tian,Juanyan Wu,Junbin Gao,Jiamiao Jiang,Kun Liu,Shuanghu Wang,Fei Wang,Fei Tong,Yicheng Ye,Lu Liu,Bin Chen,Xing Ma,Xuncai Chen,Fei Peng,Yingfeng Tu
Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous H2O2 into toxic ·OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO2 nanoparticles with catalytic activity for active Fenton-like Mn2+ delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn2+ is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on ·OH, thereby leading to enhanced cancer CDT. The as-developed MnO2-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2021
·Vol. 9
·期 45
·9413-9422
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IF 6.331
Min Liu,Hongshuai Wu,Senlin Wang,Jinzhong Hu,Baiwang Sun
The integration of metal-ion therapy and hydroxyl radical (˙OH)-mediated chemodynamic therapy (CDT) holds great potential for anticancer treatment with high specificity and efficiency. Herein, Ag nanoparticles (Ag NPs) were enveloped with Cu2+-based metal–organic frameworks (MOFs) and further decorated with hyaluronic acid (HA) to construct a glutathione (GSH)-activated nanoplatform (Ag@HKU-HA) for specific chemodynamic/metal-ion therapy. The obtained nanoplatform could avoid the premature leakage of Ag in circulation, but realize the release of Ag at the tumor site owing to the degradation of external MOFs triggered by Cu2+-reduced glutathione. The generated Cu+ could catalyze endogenous H2O2 to the highly toxic ˙OH by a Fenton-like reaction. Meanwhile, Ag NPs were oxidized to toxic Ag ions in the tumor environment. As expect, the effect of CDT combined with metal-ion therapy exhibited an excellent inhibition of tumor cells growth. Therefore, this nanoplatform may provide a promising strategy for on-demand site-specific cancer combination treatment.
研究领域:
纳米医学
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癌症治疗
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材料科学
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生物医学工程
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化学生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2022
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IF 8.008
Zizhong Yang,Birong Liu,Ting Huang,Bao-Ping Xie,Wen-Jun Duan,Min-Min Li,Jin-Xiang Chen,Jun Chen,Zong Dai
Sensitive and specific imaging of microRNA (miRNA) in living cells is of great value for disease diagnosis and monitoring. Hybridization chain reaction (HCR) and DNAzyme-based methods have been considered as powerful tools for miRNA detection, with low efficient intracellular delivery and limited amplification efficiency. Herein, we propose a Hairpins@MnO2 nanosystem for intracellular enzyme-free exponential amplification for miRNA imaging. The enzyme-free exponential amplification is based on the synergistic cross-activation between HCR and DNAzymes. The MnO2 nanosheets were employed as the carrier of three kinds of hairpin DNA probes and further provided appropriate Mn2+ as DNAzyme cofactors in the living cell. Upon entering cells and in the presence of highly expressed glutathione (GSH) in tumors, MnO2 is reduced to release Mn2+ and the three kinds of hairpin DNA probes. In the presence of target miRNA, the released hairpin DNA H1 and H2 probes self-assemble via HCR into the wire-shaped active Mn2+-based DNAzymes which further catalyze the cleavage of H3 to generate numerous new triggers to reversely stimulate HCR amplifiers, thus offering tremendously amplified Förster resonance energy transfer readout. The method has a detection limit of 33 fM, which is 2.4 × 104 times lower than that of the traditional HCR system. The developed method also has a high specificity; even miRNAs with a single base difference can be distinguished. Live cell imaging experiments confirmed that this Hairpins@MnO2 nanosystem allows accurate differentiation of miRNA expression of cancer cells and normal cells. The method holds great potential in biological research of nucleic acids.
研究领域:
生物化学
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分子生物学
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纳米技术
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癌症诊断
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DOI
PubMed
高影响因子
Nano Today
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2024
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IF 13.2
Fanqiang Bu,Mengnan Liu,Wangtao Zhao,Fang Liu,Wensheng Xie,Guofeng Li,Xing Wang
Combating bacterial biofilm poses a significant challenge because of the dense extracellular polymeric substance (EPS) barrier and inherent drug tolerance. Herein, the designed core-shell nanoparticles (DA 3 -NPs) that eradicate biofilm by precise in-situ phototherapy are reported. DA 3 -NPs are self-assembled using thermosensitive azo-polymers (AP 3 ) to encapsulate GSH-degradable phototherapeutic polymers (DBP) via charge interaction. Notably, D -aminoalanine grafted onto the AP 3 serves as a critical component, providing an electroneutral shell and bacterial peptidoglycan targeting ability to the DA 3 -NPs. Consequently, DA 3 -NPs effectively penetrate EPS up to a depth of 60 µm and precisely target the bacteria within the biofilms. Upon exposure to laser irradiation and the GSH microenvironment, DA 3 -NPs undergo sequential responses involving shell detachment and core disintegration. These processes facilitate point-to-point bacterial killing through the in-situ generations of ROS, carbon radicals and heat damage to the internal bacteria. Compared to non-targeted nanoparticles, DA 3 -NPs exhibit a 61-fold increase in biofilm removal efficiency. This study thus presents a precise in-situ phototherapy strategy for nonantibiotic treatment of biofilm infections.
研究领域:
纳米技术
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生物医学工程
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微生物学
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药学
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DOI
高影响因子
DYES AND PIGMENTS
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2021
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IF 4.889
Jie Zhang,Haishuang Jia,Wenfang Liu,Jun Wang,Dawei Fang
Cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and hydrogen sulfide (H 2 S) are essential active substance in human body. The identification and detection of biothiols and H 2 S are of great significance for the early diagnosis of certain diseases. In this paper, a new dual excitation and dual emission fluorescent probe , carbon quantum dot-O-7-nitrobenzo-2-oxa-1,3-diazole (CQDs-O-NBD), for the detection of biothiols and H 2 S was synthesized. The carbon quantum dots (CQDs-OH) (λ ex/em maxima = 377 nm/467 nm) were synthesized by a microwave-assisted method using hydroquinone as the carbon source. Through the reaction of the phenolic hydroxyl group of the carbon quantum dots and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl), the CQDs-O-NBD was synthesized. Due to the static quenching (SQ) and the photo-induced electron transfer (PET) from CQDs to NBD, the fluorescence of the CQDs-O-NBD is very weak. After adding biothiols and H 2 S, the ether bond of the CQDs-O-NBD was broken through nucleophilic substitution reaction , which led to the release of the CQDs-OH (channel 1 is turned on) and generation of a new compound NBD-thiols (channel 2). The CQDs-O-NBD as a probe shows the high selectivity and sensitivity for Cys/Hcy/GSH/NaHS (LOD of 0.24 μM/0.21 μM/0.19 μM/0.18 μM) over other aminos and ions by channel 1. The new formed compounds from NBD and Cys/Hcy have strong fluorescence under 470 nm wavelength light excitation (channel 2 is turned on), while the formed compounds from NBD and GSH/NaHS have no fluorescence (no channel 2), so the CQDs-O-NBD can discriminate Cys/Hcy (LOD: 0.07 μM/0.06 μM) from GSH/NaHS. In addition, the CQDs-O-NBD shows low toxicity and can be applied to the detection of Cys in fetal bovine serum and imaging in living cells.
研究领域:
分析化学
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生物化学
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生物医学工程
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DOI
高影响因子
Biochemistry and Cell Biology
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2024
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IF 2.4
Xiang Chen,Yuan Yao,Guotong Gong,Tianji He,Chenjun Ma,Jingsong Yu
Prostate cancer (PCa) is a complex disease with diverse molecular alterations. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits pleiotropic roles in PCa, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR. While targeting ferroptosis is an innovative PCa therapeutic strategy, the impact of AhR on this process remains unclear. This study aimed to investigate the influence of AhR on lipid peroxidation and ferroptosis. Results showed that TCDD activated AhR, as evidenced by increased CYP1A1 expression, leading to reduced cell viability. TCDD caused mitochondria shrinkage, decreased the GSH/GSSG ratio, and elevated the MDA levels and lipid peroxidation. Interestingly, AhR knockdown reversed these effects, similar to the action of ferroptosis inhibitors. Mechanistically, TCDD suppressed nuclear receptor subfamily 4 group A member 1 (NR4A1) expression, in part due to AhR activation. This suppression subsequently led to a reduction in the expression of the NR4A1 downstream target stearoyl-CoA desaturase 1 (SCD1). NR4A1 overexpression counteracted the effects of TCDD. In vivo, TCDD activated AhR, downregulated NR4A1 and SCD1 expression, induced mitochondria shrinkage, and increased the MDA and 4-hydroxynonenal (4-HNE) levels. In summary, TCDD promotes ferroptosis in androgen-dependent PCa via inhibiting the NR4A1/SCD1 axis, in part dependent on AhR activation.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2017
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IF 5.401
Jing Chen,Qin Ma,Xiaoyan Hu,Yunjing Gao,Xiaoyu Yan,Dongdong Qin,Xiaoquan Lu
In the present work, we proposed a novel naked-eye and turn-on fluorescence sensor based on the 5,10,15,20-(4-sulphonatophenyl) porphyrin (TPPS 4 )-Hg 2+ system with short assay time and high sensitivity to detect glutathione (GSH) in real samples. The TPPS 4 was the first time to detect GSH because of its high fluorescence quantum yield. The initial fluorescence from TPPS 4 was quenched by Hg 2+ with an electron transfer process. However, when put a certain concentration of GSH into this system, the fluorescence sensor was turned to the “on” state, which was related to a competitive affinity of Hg 2+ to GSH and the N atoms of porphyrin ring. Under the optimal conditions, the naked-eye detection limit was 0.43 nM and the limit of detection (LOD) was arrived to 16 fM (S/N = 3) for GSH. The linear regions are obtained by two ranges varying from 0 to 28.5 μM and from 38.15 to 61.87 μM. Furthermore, it was confirmed that the TPPS 4 -Hg 2+ fluorescence probe has excellent selectivity, high sensitivity and quick fluorescence response for GSH.
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产品关联
DOI
高影响因子
LIFE SCIENCES
·
2024
·
IF 5.2
Qiuwen Fei,Jian Zhang,Liangqiong Chen,Manqi Shi,Qinglan Wang,Feifan Xu,Jiahai Shi,Yongwei Qin
Background Mycobacterium tuberculosis infection triggers various forms of host cell death, including ferroptosis in lung epithelial cells; YY1, a critical transcription factor, plays a pivotal role in regulating ferroptosis, however, the underlying mechanisms are not fully understood. Methods To investigate Mycobacterium marinum ( M.marinum )infection in lung epithelial cells A549 and H1299, we utilized flow cytometry to evaluate cell death and measure reactive oxygen species (ROS). Colony-forming unit (CFU) assays determined the intracellular bacterial load. Ferroptosis was analyzed using a specific detection kit to measure malondialdehyde (MDA) and glutathione (GSH) levels. The interaction between the transcription factor YY1 and the iNOS promoter was assessed through a dual-luciferase reporter assay. Results M.marinum induced ferroptosis in lung epithelial cells through invasion. This effect is most pronounced at 8 h of infection and decreases over time but increased with a higher multiplicity of infection (MOI). YY1 knockdown decreases the expression of SLC7A11 and GPX4, attenuates cellular ferroptosis, while YY1 overexpression has the opposite phenomenon, enhancing the expression of bactericidal molecules such as iNOS and MPEG1, thereby markedly reducing the intracellular bacterial load. We identified substantial binding of YY1 to the iNOS promoter region (−655 to −1018 bp), enhancing mycobactericidal activity in YY1-overexpressing cells. Conclusions Our study demonstrates that YY1 inhibits ferroptosis induced by Mycobacterium marinum infection and reduces intracellular bacterial proliferation in lung epithelial cells. These findings provide a crucial basis for developing anti-tuberculosis therapies that target YY1 modulation, potentially offering new clinical avenues for the treatment of tuberculosis.
研究领域:
微生物学
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细胞生物学
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传染病学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
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IF 3.571
Danmei Tian,Fangfang Wang,Menglong Duan,Lingyun Cao,Youwei Zhang,Xinsheng Yao,Jinshan Tang
Seven new coumarin analogues (1, 2, and 4–8), together with ten known analogues (3, 9–17), were isolated from the air-dried pericarp of Citrus grandis. The structures of these compounds were determined by HR-ESI-MS, UV/vis, and 1D- and 2D-NMR spectra. Meanwhile, the hepatoprotective activities of all these coumarins were evaluated by MTT assays using the d-galactosamine-induced LO2 cell injury model. The results show that compounds 3 and 4 exhibited the strongest hepatoprotective activities. Moreover, compounds 3 and 4 suppressed increases in the levels of alanine transaminase (ALT) and aspartate transaminase (AST) in d-galactosamine-treated LO2 cells, further confirming the hepatoprotective effects of these compounds. Mechanistically, compounds 3 and 4 increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the level of malondialdehyde (MDA) in injured LO2 cells induced by d-galactosamine. These findings shed light on a better understanding of the hepatoprotective effect of Citrus grandis, providing novel insights into the development of coumarin-based hepatoprotective drugs in the future.
研究领域:
药理学
·
天然产物化学
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肝病学
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DOI
PubMed
高影响因子
Polymer Chemistry
·
2021
·Vol. 12
·期 12
·1768-1775
·
IF 5.582
Jamshid Kadirkhanov,Cheng-Lin Yang,Zi-Xuan Chang,Ren-Man Zhu,Cai-Yuan Pan,Ye-Zi You,Wen-Jian Zhang,Chun-Yan Hong
In comparison with the post-polymerization cross-linking strategy, in situ cross-linking by divinyl comonomers in polymerization-induced self-assembly (PISA) is a more straightforward and convenient approach to produce structurally stabilized nano-objects. However, cross-linking usually lowers the chain mobility and hence prevents morphology transition, so formation of higher order morphologies (worm-like micelles or vesicles) by the in situ cross-linking strategy in PISA has always been a great challenge. In this work, not only cross-linked structures but also a promoting effect on morphology transition has been observed during the in situ cross-linking PISA. Worm-like micelles, lamella and vesicles with stabilized (cross-linked) structures are produced by RAFT dispersion copolymerization of 2-(diisopropylamino)ethyl methacrylate (DIPEMA) and the divinyl comonomer cystaminebismethacrylamide (CBMA). The morphology transition is not prevented due to the slower consumption of CBMA than that of the DIPEMA, and the cross-linking process is mostly delayed to the late stage of polymerization. What is surprising, compared with RAFT dispersion polymerization of DIPEMA in the absence of CBMA, is that polymeric nano-objects with higher order morphologies are generated in most cases of the RAFT dispersion copolymerization of DIPEMA and CBMA. The slower consumption of CBMA generates branched structures of the solvophobic blocks, which significantly promote the morphology transition. Cleavage of the cross-linkers (disulfide linkage) by incubating with glutathione (GSH) leads to the morphology transition of the nano-objects to the lower order ones, which further demonstrates the promoting effect on morphology transition in in situ cross-linking PISA.
研究领域:
高分子化学
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材料科学
·
纳米技术
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）