Advanced Healthcare Materials
·
2025
·
IF 9.6
Chen-Song Huang,Chunlei Dai,Qi Liu,Si-Yun Chen,Ya-Hao Guo,Jie-Qin Wang,An-Da Zheng,Xi-Tai Huang,Jun Wu,Xiao-Yu Yin
Ferroptosis has emerged as a critical mechanism in overcoming drug resistance in various tumors; however, its role in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly explored. Additionally, the effectiveness of ferroptosis in many cancer therapies has been limited. In our study, we found that GPX4 is upregulated in gemcitabine-resistant (GR) PDAC patient tissues and cell lines. Notably, inhibiting GPX4 can reverse gemcitabine resistance in PDAC through the induction of ferroptosis, highlighting it as a potential therapeutic target. To address this, we developed a novel nanomedicine, GSH-depleted and ferroptosis-induced (FiN), designed to encapsulate and deliver the GPX4 inhibitor RSL3, resulting in a dual ferroptosis-induced nanomedicine (DFiN). In a PDAC patient-derived xenograft (PDX) mouse model exhibiting gemcitabine resistance, DFiN demonstrated significant accumulation in GR PDAC tumors, leading to a reduction in intracellular GSH levels and inhibition of GPX4. This dual action promoted lipid peroxidation and synergistically induced ferroptosis, effectively reversing gemcitabine resistance. Both in vitro and in vivo experiments confirmed that DFiN is effective in overcoming gemcitabine resistance in GR PDAC cells and PDX tumors, with minimal toxicity observed. This study presents a promising strategy for addressing drug resistance in cancer therapy.
研究领域:
肿瘤学
·
纳米医学
·
分子生物学
·
癌症治疗
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Methods
·
2022
·Vol. 6
·期 6
·2200178
·
IF 15.367
Rui Xu,Phei Er Saw,Lei Xu
Two-dimensional (2D) nanomaterials have attracted increasing attention in cancer theranostics due to their ultrahigh specific surface area resulting in more radicals and/or reactive oxygen species (ROS) generation in chemodynamic therapy (CDT). However, their biomedical prospects are greatly limited by poor biocompatibility, low dispersion, weak stability, and the potential threat of their high immunogenicity. Moreover, rapid depletion of ROS by the high level of antioxidants (e.g., glutathione) in cancer cells severely limits the therapeutic effects of cancer CDT. Herein, a robust method is developed to improve the biomedical application of 2D nanomaterials via constructing a 2D nanomaterials delivery nanoplatform with hemoglobin-based minerals biological coat for the safe encapsulation, long blood circulation, and controlled release of 2D nanomaterials. After intravenous administration and then internalization by cancer cells, the acidic microenvironment and high concentration of H 2 O 2 can trigger rapid release of Cu-T nanoscale metal-organic frameworks (nMOFs) from Cu-T@MH. Then, the released Cu-T nMOFs with simultaneous high ROS production and GSH depletion endow the Cu-T@MH nanoplatform with enhanced cancer CDT. Besides, the fluorescence recovery of tetrakis(4-carboxyphenyl) porphyrin in Cu-T nMOFs during the GSH depletion process can accurately visualize the cancer therapeutic action.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2026
·
IF 4.8
Yunxiang Qi,Zhenghua Zhang,Xuan Wang,Haitao Long,Lumei Pu,Weibing Xu
Smart nanopesticides demonstrates excellent potential in the prevention of tomato gray mold. Herein, temperature, pH and GSH triple responsive of pyraclostrobin nanopesticide (CDC-F127-P) is fabricated base on Pluronic F127 and cinnamaldehyde-derived liposome. The maximum fungicide loading of Pyr reaches 52.9%. The particle size and zeta potential are 143 nm and + 29 mV. The release of Pyr increases from 38% to 61% after 48 h as the temperature rises from 5 °C to 35 °C. The value increases from 62% to 87% when the concentration of oxalic acid rises from 0 to 20 mM, which increases from 10% to 37% as the concentration of GSH rises from 0 to 20 mM. The EC₅₀ of CDC-F127-P is 1.96 μg/mL. The inhibition rates of CDC-F127-P for mycelial growth and spore germination are 69.3% and 73.0% at 10 μg/mL. The nucleic acid and protein leakage reaches 124.8 μg/mL and 113.5 μg/mL. A spore mortality rate of 66.4% is arrived. Mitochondrial membrane potential reduces by 96% after treatment with 2 μg/mL. The CDC-F127-P shows a hemolysis rate of 1.8% and a tomato seed germination rate of 60% at 10 μg/mL. The contact angle on the tomato leaf is 74.0 o . A solution retention capacity of 27.5 mg/cm 2 is retained after simulated rainfall. The disease inhibition rates of 64.9% and 71.0% in detached-leaf and potted-plant assays after treatment with 10 μg/mL CDC-F127-P. The triple-responsive CDC-F127-P nanopesticide offers a highly efficient and safe strategy for gray mold control and presenting a novel approach for developing green nano-pesticides.
✓ 已验证
DOI
高影响因子
Journal of Analysis and Testing
·
2022
·Vol. 7
·期 2
·147-156
·
IF 0
Yang Xiaohua,Zhang Peigang,Tan Jie,Li Xuebing,Zhang Weidong,Bian Wei,Choi Martin M. F.
Owing to the excellent stability, biocompatibility and photoluminescence property, graphene quantum dots (GQDs) are emerging as a kind of potential materials to be applied in a series of fields ranging from sensor to drug delivery. As the growing concern for human and environmental safety, selective detection of metal ions has been paid more and more attention. GQDs, as nanoparticles with superior optical properties, have been attracting growing attention in the field of metal ions detection. In this work, glutathione(GSH) functionalized boron doped graphene quantum dots (B-GQDs@GSH) were successfully synthesized with stable bright blue fluorescence and has been used for the detection of Fe 3+ . A good linear relationship between 1/( F 0 ‒ F ) and 1/ c with the concentration ranging from 0.70 to 53 μmol/L was obtained with a detection limit of 5.5 nmol/L. The application of B-GQDs@GSH for Fe 3+ detection in water samples was demonstrated and the quenching mechanism was further explored. Due to low cytotoxicity and favorable biocompatibility, B-GQDs@GSH were successfully applied for cell fluorescence imaging and intracellular determination of Fe 3+ .
✓ 已验证
产品关联
DOI
FOOD CHEMISTRY
·
2023
·
IF 8.8
Xiaoyang Wang,Huajie Yu,Qiuhong Li,Yuhang Tian,Xiaolin Gao,Wanqi Zhang,Zhicong Sun,Yaoting Mou,Xia Sun,Yemin Guo,Falan Li
A novel dual-signal fluorescent sensor was developed for detecting organophosphorus pesticides (OPs). It relies on the catalytic activities of acetylcholinesterase (AChE) and choline oxidase (ChOx) to generate hydrogen peroxide (H 2 O 2 ) through the conversion of acetylcholine (ACh) to choline·H 2 O 2 then oxidizes ferrocene-modified tetraphenylethylene (TPE-Fc) to its oxidized state (TPE-Fc + ), resulting in enhanced cyan fluorescence due to aggregation. Simultaneously, ferrocene oxidation generates hydroxyl radicals (•OH), causing a decrease in orange fluorescence of glutathione-synthesized gold nanoclusters (GSH-AuNCs). The presence of OPs restricts AChE activity, reducing H 2 O 2 production. Increasing OPs concentration leads to decreased cyan fluorescence and increased orange fluorescence, enabling visual OPs detection. The sensor has a linear dynamic range of 10–2000 ng/mL with a detection limit of 2.05 ng/mL. Smartphone-based color identification and a WeChat mini program were utilized for rapid OPs analysis with successful outcomes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Xiao Zhao,Ying Wang,Tingting Zhu,Huili Wu,Diya Leng,Zhiguo Qin,Yan Li,Daming Wu
Background Mesoporous calcium-silicate nanoparticles (MCSNs) are advanced biomaterials that have been used to control drug delivery for many years. Ultrasmall Prussian blue nanoparticles (UPBNPs) showed high peroxidase and catalase-like activities. This study evaluated the antibacterial and antibiofilm properties, mechanism and cytotoxicity of UPBNPs-MCSNs composites synthesized by both as precursors. Methods UPBNPs-MCSNs were prepared and characterized. The antibacterial effect of UPBNPs-MCSNs was evaluated by the MTT assay and CFU counting method, and their biosafety was tested by CCK8. Then explore the antibacterial mechanism, including TEM observation of bacterial morphology, and detection of bacterial ROS, LPO and GSH levels. The antibiofilm activity of UPBNPs-MCSNs was tested by E. faecalis biofilm model in human roots. The roots were pretreated with materials and cultured with E. faecalis , and the survival of E. faecalis on the root canal wall was observed by SEM and CLSM. Results The results showed that UPBNPs-MCSNs had potent antibacterial and antibiofilm activities. They can aggregate on the dentin surface and significantly inhibit E. faecalis adhesion and colonization. Their antibacterial activity is as effective as NaClO and calcium hydroxide (CH), can significantly prolong the time of bacterial colonization than CH, but have lower cytotoxicity to normal cells. We found that UPBNPs-MCSNs trigger a like classic ferroptosis pathway in bacteria. UPBNPs-MCSNs can induce bacteria to produce ROS and LPO, and reduce GSH level. Moreover, we observed that the metal ions chelator and the antioxidant could block their antibacterial activity. Conclusion These results reveal that UPBNPS-MCSNs have high antibacterial and antibiofilm, and can mediate the bacterial redox pathway ROS/GSH like the classical pathway of ferroptosis, providing a theoretical basis for them to develop into a safe and effective novel root canal disinfectant.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Yu Zhou,Chengyu Zhang,Yuefei Wang,Jiaxing Zhang,Xiaohui Yan,Shengping You,Wei Qi,Rongxin Su,Zhimin He
Nanotechnology has been widely used in cancer treatment but only a small fraction (0.7 %) of the administered nanoparticle was delivered into a solid tumor, while the remaining fraction causes off-target toxicity in healthy tissues. The activation of prodrugs by exogenous enzymes can be used as an effective anticancer strategy to reduce systemic toxicity. In this study, the [email protected] imidazolate framework-8 ( [email protected] ) enzyme-activated prodrug system was created based on the high catalytic activity of LA in an acidic environment and the pH response (pH∼5.5) of ZIF-8. Quercetin (QU) was selected as the prodrug, which is non-toxic and even beneficial without being activated by LA. LA could be precisely released in the acidic tumor microenvironment for activating nontoxic QU successfully to produce toxic oxidized quercetin (OQU), and the LA was steady loaded on the [email protected] under physiological conditions (pH∼7.4). Especially, the high concentrations of glutathione (GSH) in tumors could accelerate the oxidation of QU by LA. Meanwhile, GSH could be consumed continuously by the reduction of OQU for regenerating QU, thus a LA-QU-GSH redox was formed ingeniously. Therefore, the synergistic effect of OQU toxicity and GSH depletion induced reactive oxygen species (ROS) accumulation and tumor cell apoptosis. Overall, the [email protected] prodrug system provides ideas for safe and effective cancer treatment with low off-target toxicity.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
·
2019
·
IF 3.261
Yutao Yang,Xueli Yang,Keyan Zhou,Ming Jin,Wei Li
A new near-infrared (NIR) fluorescent probe based on 2-Methylchromone was exploited for relay recognition of Cu 2+ and biothiols. The mechanism involved in complex between metal ion and probe, and subsequent displacement reaction, which make the probe can detect GSH by NIR fluorescence turn on emission. Probe showed a fluorescence band at 718 nm in PBS-EtOH (3:2, v/v, 10 mM PBS, pH 7.4) solution. Upon the addition of Cu 2+ , a large fluorescence quenching was observed due to the coordination between probe 1 and Cu 2+ . The 1 -Cu 2+ could be used to detect biothiols utilizing high affinity of biothiols with Cu 2+ . This “on-off-on” fluorescent probe was also successfully applied to image GSH in MCF-7 cells and zebrafish.
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xiao-Meng Liu,Zhen-Zhen Zhu,Xin-Rui He,Yun-Hong Zou,Qian Chen,Xiao-Ya Wang,Hui-Mei Liu,Xin Qiao,Xu Wang,Jing-Yuan Xu
Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Jiayi Li,Kaifan Zheng,Luping Lin,Mengdi Zhang,Ziqi Zhang,Junyu Chen,Shaoguang Li,Hong Yao,Ailin Liu,Xinhua Lin,Gang Liu,Bing Chen
Cancer immunotherapy offers significant clinical benefits for patients with advanced or metastatic tumors. However, immunotherapeutic efficacy is often hindered by the tumor microenvironment's high redox levels, leading to variable patient outcomes. Herein, a therapeutic liposomal gold nanocage (MGL) is innovatively developed based on photo-triggered hyperthermia and a releasable strategy by combining a glutathione (GSH) depletion to remodel the tumor immune microenvironment, fostering a more robust anti-tumor immune response. MGL comprises a thermosensitive liposome shell and a gold nanocage core loaded with maleimide. The flexible shell promotes efficient uptake by cancer cells, enabling targeted destruction through photothermal therapy while triggering immunogenic cell death and the maturation of antigen-presenting cells. The photoactivated release of maleimide depletes intracellular GSH, increasing tumor cell sensitivity to oxidative stress and thermal damage. Conversely, GSH reduction also diminishes immunosuppressive cell activity, enhances antigen presentation, and activates T cells. Moreover, photothermal immunotherapy decreases elevated levels of heat shock proteins in tumor cells, further increasing their sensitivity to hyperthermia. In summary, MGL elicited a robust systemic antitumor immune response through GSH depletion, facilitating an effective photothermal immunotherapeutic strategy that reprograms the tumor microenvironment and significantly inhibits primary and metastatic tumors. This approach demonstrates considerable translational potential and clinical applicability.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Xin Yue,Qian Lin,Xiaohang Liu,Zhaoyi Yu,Jiafeng Xu,Xuan Zhu,Jinyan Lin,Aijie Liu
The high intracellular glutathione (GSH) level, naturally hypoxic conditions within the tumor microenvironment, and limited reactive oxygen species (ROS) generation pose significant obstacles to the effectiveness of sonodynamic therapy (SDT). Overcoming these barriers through depletion of GSH and relieving hypoxia offer a promising strategy to enhance SDT effectiveness. Herein, we developed a dendritic tetra-sulfide-bridged mesoporous silica (DTSMO) that encapsulated both chlorin e6 (Ce6) and cerium via channel-limited in situ coordination and is subsequently cloaked with the macrophage cell membrane (MCM) to facilitate efficient reactive oxygen species (ROS)-based therapy via multispecies enzymatic activities. First, this nanosystem exhibited Ce(IV) ions to mimic catalase (CAT)-like activity, converting H2O2 into O2, thereby effectively alleviating tumor hypoxia. Meanwhile, the nanosystem possessed Ce (III)-based peroxidase (POD)-like activity, enabling the conversion of H2O2 into hydroxyl radicals (•OH) while simultaneously depleting GSH. Both in vitro and in vivo experiments demonstrated that GSH depletion exerted a powerful supplementary effect on CDT and SDT, achieving a tumor inhibition rate of up to 96%, without affecting normal tissues during treatment.
研究领域:
纳米医学
·
癌症治疗
·
活性氧
·
酶模拟
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Xin Ji,Qiao Tang,Peng Pang,Jianping Wu,Thomas Brett Kirk,Jiake Xu,Dong Ma,Wei Xue
Antitumor efficacy of ursolic acid (UA) is seriously limited due to its low hydrophilicity and needy bioavailability. To overcome these obstacles, chemosensitive polyspermine (CPSP) conjugated with UA and folic acid (FA) as a novel targeted prodrug was designed and successfully synthesized in this investigation. This prodrug not only showed high aqueous solubility, GSH-triggered degradation and good biocompatibility, but also exhibited better inhibition effect on the tumor cells proliferation in comparison with free UA. FA-CPSP-UA could down-regulate the generation of GSH and manifest excellent ability in enhancing antitumor efficacy. In addition, FA-CPSP-UA could inhibit the expression of MMP-9, which led to restricting MCF-7 cells migration. Taken together, the results indicated that FA-CPSP-UA, as a carrier, can efficiently deliver UA to folate receptor positive cancer cells and improve tumor therapy of UA by Chemosensitive effect.
研究领域:
肿瘤学
·
药学
·
药物递送系统
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）