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.
研究领域:
纳米技术
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癌症治疗
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药学
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生物医学工程
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2020
·Vol. 12
·期 42
·5110-5119
·
IF 2.596
Shanshan Wei,Tinghua Li,Xinyu Zhang,Hongyuan Zhang,Chunzhu Jiang,Guoying Sun
The abnormal level of Cu2+ or GSH can cause variety of neurodegenerative diseases in humans. Thus, the selective and sensitive detection of Cu2+ and GSH has inspired intensive research efforts in biological sample analysis fields. Herein, an “on–off–on” fluorescent probe based on nitrogen and sulfur co-doped carbon dots (N,S-CDs) has been successfully prepared for the detection of Cu2+ and GSH. The “turn-off” process of fluorescence in the presence of Cu2+ ions was induced by forming a non-luminescent ground state complex due to the interaction between surface groups of the probe and Cu2+ ions. Moreover, the strong coordination between GSH and Cu2+ could destroy the structure of the complex and restore the fluorescence to “turn-on”. This fluorescent probe had excellent selectivity and high sensitivity toward Cu2+ and GSH with the limits of detection (LODs) of 38 nM and 41 nM. More importantly, the as-prepared N,S-CDs served as an efficient fluorescent probe for not only detecting Cu2+ ions in lake water and tap water, and GSH in BSA solution, but also sensing Cu2+ and GSH in living cells. Therefore, these N,S-CDs could be considered as a promising fluorescence probe candidate for environmental monitoring and biological imaging.
研究领域:
分析化学
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生物化学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Zhao Wang,Bin Liu,Qianqian Sun,Shuming Dong,Ye Kuang,Yushan Dong,Fei He,Shili Gai,Piaoping Yang
The therapeutic effect of traditional chemodynamic therapy (CDT) agents is severely restricted by their weakly acidic pH and glutathione (GSH) overexpression in the tumor microenvironment. Here, fusiform-like copper(II)-based tetrakis(4-carboxy phenyl)porphyrin (TCPP) nanoscale metal–organic frameworks (nMOFs) were designed and constructed for the first time (named PCN-224(Cu)-GOD@MnO2). The coated MnO2 layer can not only avoid conjugation of glucose oxidase (GOD) to damage normal cells but also catalyzes the generation of O2 from H2O2 to enhance the oxidation of glucose (Glu) by GOD, which also provides abundant H2O2 for the subsequent Cu+-based Fenton-like reaction. Meanwhile, the Cu2+ chelated to the TCPP ligand is converted to Cu+ by the excess GSH in the tumor, which reduces the tumor antioxidant activity to improve the CDT effect. Next, the Cu+ reacts with the plentiful H2O2 by enzyme catalysis to produce a toxic hydroxyl radical (•OH), and singlet oxygen (1O2) is synchronously generated from combination with Cu+, O2, and H2O via the Russell mechanism. Furthermore, the nanoplatform can be used for both TCPP-based in vivo fluorescence imaging and Mn2+-induced T1-weighted magnetic resonance imaging. In conclusion, fusiform-like PCN-224(Cu)-GOD@MnO2 nMOFs facilitate the therapeutic efficiency of chemodynamic and starvation therapy via combination with relief hypoxia and GSH depletion after acting as an accurate imaging guide.
研究领域:
材料科学
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纳米技术
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生物医学工程
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癌症研究
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诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 18
·期 9
·2105465
·
IF 13.281
Jiayu Xiao,Luo Hai,Yaoyao Li,Huan Li,Minhui Gong,Zefeng Wang,Zifeng Tang,Le Deng,Dinggeng He
Nanozyme-based chemodynamic therapy (CDT) for fighting bacterial infections faces several major obstacles including low hydrogen peroxide (H 2 O 2 ) level, over-expressed glutathione (GSH) in infected sites, and inevitable damage to healthy tissue with abundant nonlocalized nanozymes. Herein, a smart ultrasmall Fe 3 O 4 -decorated polydopamine (PDA/Fe 3 O 4 ) hybrid nanozyme is demonstrated that continuously converts oxygen into highly toxic hydroxyl radical (•OH) via GSH-depleted cascade redox reactions for CDT-mediated bacterial elimination and intensive wound disinfection. In this system, photonic hyperthermia of PDA/Fe 3 O 4 nanozymes can not only directly damage bacteria, but also improve the horseradish peroxidase-like activity of Fe 3 O 4 decorated for CDT. Surprisingly, through photothermal-enhanced cascade catalytic reactions, PDA/Fe 3 O 4 nanozymes can consume endogenous GSH for disrupting cellular redox homeostasis and simultaneously provide abundant H 2 O 2 for improving •OH generation, ultimately enhancing the antibacterial performance of CDT. Such PDA/Fe 3 O 4 can bind with bacterial cells, and reveals excellent antibacterial property against both Staphylococcus aureus and Escherichia coli . Most interestingly, PDA/Fe 3 O 4 nanozymes can be strongly retained in infected sites by an external magnet for localized long-term in vivo CDT and show minimal toxicity to healthy tissues and organs. This work presents an effective strategy to magnetically retain the therapeutic nanozymes in infected sites for highly efficient CDT with good biosafety.
研究领域:
纳米技术
·
生物医学工程
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材料科学
·
化学
·
细菌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2020
·
IF 3.232
Jun Zhang,Huan Yang,Shuang Pan,Hui Liu,Xiaoli Hu
In this study, a new “off-on-off” fluorescence strategy for detecting glutathione (GSH) and silver ions (Ag + ) is presented. The constructed nanoprobe is composed of B, N co-doped carbon dots (B, N-CDs) and manganese dioxide nanosheets (MnO 2 nanosheets), where MnO 2 nanosheets serve as a kind of efficient fluorescence quencher . The sensing mechanism of the system is based on the inner filter effect (IFE) and destruction-protection strategy. The assay strategy includes three processes: fluorescence quenching of B, N-CDs by MnO 2 nanosheets, the deconstruction of MnO 2 nanosheets by GSH, the combination between GSH and Ag + . The MnO 2 nanosheets are reduced to Mn 2+ because of the addition of GSH and restoring the fluorescence intensity of the system, while the formation of the complex between GSH and Ag + inhibit the reduction of MnO 2 nanosheets on account of the addition of Ag + , leading to the decrease in fluorescence of the probe. This strategy allows the quantitative detection of GSH and Ag + with detection limit of 0.32 μmol·L −1 and 0.24 μmol·L −1 , respectively. Moreover, this approach displays good sensitivity, selectivity and broad linear range, which could be broadly applicable for practical applications.
研究领域:
分析化学
·
纳米技术
·
荧光传感
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Huidong Wang,Jiadong Guo,Yangzi Yang,Ning Wang,Xiao Yang,Liang Deng,Xiankun Cao,Zhaoyang Ran,Dong Fang,Kang Xu,Yingchun Zhu,Jie Zhao,Jingke Fu,Yongqiang Hao
With the clinical prevalence of drug-resistant pathogenic bacteria, developing non-antibiotic strategies to treat multi-drug-resistant bacterial infections is urgent yet challenging. Ferroptosis is a non-apoptotic form of regulated cell death that can overcome drug resistance. Emerging evidence shows the potential of triggering ferroptosis-like for anti-infection therapy, but the direct delivery of iron species is inefficient and may cause detrimental effects. Herein, CuFeS 2 nanozyme is revealed as a ferroptosis-like initiator to eradicate bacterial infections for effective anti-infection therapy. Upon activating by visible light irradiation or hydrogen peroxide, the as-prepared CuFeS 2 nanozyme can significantly expedite reactive oxygen species generation, deplete intracellular glutathione, and interfere with respiratory metabolisms, resulting in lipid peroxidation-driven ferroptotic damage. Additionally, the CuFeS 2 displays good photothermal conversion capacity under near-infrared light irradiation, further augmenting the antibacterial efficiency. Accordingly, the CuFeS 2 nanozyme shows potent antibacterial activity against Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro . Moreover, it shows excellent biocompatibility and robust anti-infection effects in MRSA-infected wounds in vivo . This ferroptosis-like antibacterial strategy may open up new insights into the treatment of drug-resistant pathogen infection.
研究领域:
纳米技术
·
生物医学工程
·
微生物学
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药学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Junqin Li,Mengya Sun,Xiaoxian Tang,Yuqian Liu,Chunlei Ou,Yuze Luo,Li Wang,Luo Hai,Le Deng,Dinggeng He
Reactive oxygen species (ROS) are widely considered to the effective therapeutics for fighting bacterial infections especially those associated with biofilm. However, biofilm microenvironments including hypoxia, limited H 2 O 2 , and high glutathione (GSH) level seriously limit the therapeutic efficacy of ROS-based strategies. Herein, we have developed an acidic biofilm microenvironment-responsive antibacterial nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO 2 ) synthesized in situ and indocyanine green (ICG). The three-in-one nanotherapeutics (CuO 2 /ICG@CBSA) are capable of releasing Cu 2+ and H 2 O 2 in a slightly acidic environment, where Cu 2+ catalyzes the conversion of H 2 O 2 into hydroxyl radical (•OH) and consumes the highly expressed GSH to disrupt the redox homeostasis. With the assistance of an 808 nm laser, the loaded ICG not only triggers the production of singlet oxygen ( 1 O 2 ) by a photodynamic process, but also provides photonic hyperpyrexia that further promotes the Fenton-like reaction for enhancing •OH production and induces thermal decomposition of CuO 2 for the O 2 -self-supplying 1 O 2 generation. The CuO 2 /ICG@CBSA with laser irradiation demonstrates photothermal-augmented multi-mode synergistic bactericidal effect and is capable of inhibiting biofilm formation and eradicating the biofilm bacteria. Further in vivo experiments suggest that the CuO 2 /ICG@CBSA can effectively eliminate wound infections and accelerate wound healing. The proposed three-in-one nanotherapeutics with O 2 /H 2 O 2 -self-supplied ROS generating capability show great potential in treating biofilm-associated bacterial infections. Statement of Significance Here, we have developed an acidic biofilm microenvironment-responsive nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO 2 ) synthesized in situ and indocyanine green (ICG). The nanotherapeutics (CuO 2 /ICG@CBSA) are capable of releasing Cu 2+ and H 2 O 2 in an acidic environment, where Cu 2+ catalyzes the conversion of H 2 O 2 into •OH and consumes the overexpressed GSH to improve oxidative stress. With the aid of an 808 nm laser, ICG provides photonic hyperpyrexia for enhancing •OH production, and triggers O 2 -self-supplying 1 O 2 generation. CuO 2 /ICG@CBSA with laser irradiation displays photothermal-augmented multi-mode antibacterial and antibiofilm effect. Further in vivo experiments prove that CuO 2 /ICG@CBSA effectively eliminates wound infection and accelerates wound healing. The proposed three-in-one nanotherapeutics show great potential in treating biofilm-associated bacterial infections.
研究领域:
纳米技术
·
生物材料
·
生物医学工程
·
微生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2017
·
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.
研究领域:
分析化学
·
材料科学
·
生物化学
✓ 已验证
产品关联
DOI
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.
研究领域:
癌症免疫治疗
·
纳米技术
·
生物医学工程
·
药学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2022
·
IF 6.814
Chunhong Mo,Zhao Wang,Jianying Yang,Yiqiang Ouyang,Qian Mo,Shuting Li,Ping He,Limin Chen,Xinchun Li
Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity . MoS 2 nanosheets were synthesized and modified by α ν β 3 integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier . Further, covalent coupling of antitumor drug , thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS 2 /DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment . The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.
研究领域:
纳米技术
·
药学
·
癌症研究
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaoyu Zhao,Chenglong Xue,Yu Liu,Tao Wang,Qi Shuai
The treatment of diabetic wounds remains a challenge due to the interaction between hyperglycemia, immune imbalance and bacterial infection. Herein, we developed a Glu and GSH double-unlocked immunomodulatory nanocascade reactor to accelerate diabetic wounds healing which dynamically manages the wound microenvironment by controlling blood glucose levels, restoring immune regulation and eliminating bacteria. On the one hand, ultra-small gold nanoparticles with GOx activity can catalyse glucose at the diabetic wound site, which can be further enhanced by photothermal effects, thus destroying bacterial biofilm structures, reversing wounds pH, and reducing bacterial reproduction. On the other hand, the sustained controlled release of NO at specific sites was achieved by depleting over-expressed GSH in the wounds to restore normal immune regulation, which not only promotes M2 macrophage polarisation and expressions of anti-inflammatory factors such as IL-10 and TGF-β1, but also produces VEGF and CD31 via the PI3K/AKT signalling pathway. Especially, the chemical resonance energy transfer (CRET) strategy was first applied to diabetic wounds treatment, achieving chemical photodynamic therapy (PDT) while reducing the secondary tissue damage caused by catalytically-generated H 2 O 2 . In summary, the nanocascade reactor provides a new reference for bacterialy-infected diabetic wounds treatment mode by reducing blood glucose and restoring immune regulation in parallel.
研究领域:
纳米技术
·
免疫学
·
伤口愈合
·
糖尿病
·
细菌学
·
生物化学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 5.9
Kan Li,Shengbin Gui,Ningning Wang,Xiao Li,Chunqin Zhao,Mingyu Liu,Zhen Zhang
Intravenously administered nanoparticles (NPs) often bind with plasma proteins, forming protein corona that prompt rapid systemic clearance, a primary challenge in nanomedicine. In this study, we developed a pH- and GSH-sensitive “stealth” nanodelivery system, PTX@NPs-aPD1-IL, for sequential drug release. By using a biocompatible choline-based ionic liquid (IL) as the coating for NPs, the interaction and adsorption of NPs with serum proteins were reduced, achieving targeted delivery to the lung organ and increasing drug accumulation. In the weakly acidic extracellular tumor microenvironment (pH 6.5), the anti-PD-1 antibody (aPD-1) was first released to block the PD-1/PD-L1 pathway and restore the immunocidal function of T cells. In the highly reductive intracellular environment of tumor cells, the disulfide bonds were cleaved, causing NPs to rupture and release paclitaxel (PTX). It induced tumor cell apoptosis and triggered immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation and activated T cells for chemo-immunotherapy. In the mouse orthotopic lung cancer model, PTX@NPs-aPD1-IL exhibited superior efficacy to other treatment groups at the same dose. This was due to the significantly increase in the release of immune factors, including TNF-α and IFN-γ, and the promotion of CD8 + T cells recruitment, which induced a stronger immune response, and thus enhanced the anti-lung cancer effect. In summary, PTX@NPs-aPD1-IL provided a promising strategy for effective chemo-immunotherapy for lung cancer through sequential release profile.
研究领域:
纳米医学
·
肿瘤学
·
药学
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）