COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
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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
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药学
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药物递送系统
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癌症治疗
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 15
·2202280
·
IF 10
Wenya Li,Rongtian Li,Qiang Ye,Yiming Zou,Xing Lu,Wenhua Zhang,Jinxiang Chen,Yinghua Zhao
Nanomedicine exhibits emerging potentials to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC). Nevertheless, it is still difficult to develop a precise codelivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 is selected as the carrier to enable effective cancer therapy through light-activated reactive oxygen species (ROS) formation, and the PCN-224@Mn 3 O 4 @HA is created in a simple one-step process by coating Mn 3 O 4 nanoshells on the PCN-224 template, which can then be used as an “ROS activator” to exert catalase- and glutathione peroxidase-like activities to alleviate tumor hypoxia while reducing tumor reducibility, leading to improved photodynamic therapeutic (PDT) effect of PCN-224. Meanwhile, Mn 2+ produced cytotoxic hydroxyl radicals (∙OH) via the Fenton-like reaction, thus producing a promising spontaneous chemodynamic therapeutic (CDT) effect. Importantly, by remodeling the tumor microenvironment (TME), Mn 3 O 4 nanoshells downregulated hypoxia-inducible factor 1 α expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light-controlled ROS formation and multimodality imaging abilities, can effectively inhibit tumor proliferation through synergistic PDT/CDT, and prevent tumor resurgence by remodeling TME.
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PubMed
高影响因子
Small
·
2021
·Vol. 18
·期 6
·2103528
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IF 13.281
Bijiang Geng,Shuang Xu,Ping Li,Xiaokai Li,Fuling Fang,Dengyu Pan,Longxiang Shen
Sonodynamic therapy as a promising noninvasive modality is being developed for tumor therapy, but there is a lack of next-generation sonosensitizers that can generate full ROS at high yields and simultaneously deplete elevated levels of glutathione (GSH) in tumor cells. Semiconductor p-n junctions are engineered as high-efficacy sonosensitizers for sonodynamic tumor eradication using pyridine N-doped carbon dots (N-CDs) as a p -type semiconductor and oxygen-deficient TiO 2− x nanosheets as a n -type semiconductor. The rate constants of 1 O 2 and •OH generation by ultrasound-excited N-CD@TiO 2− x p-n junctions are 4.3 and 4.5 times higher than those of TiO 2 , respectively. A Z-scheme carrier migration mechanism in the p-n junction achieving the rapid spatial separation of the ultrasound-generated electron–hole pairs for enhanced full ROS production is proposed. GSH-cleavable, Pt-crosslinked, N-doped CD fluorescent probes to detect the presence of intracellular GSH are also constructed. A GSH-responsive, p-n junction platform (Pt/N-CD@TiO 2− x ) with integrated GSH detection, GSH depletion, and enhanced sonodynamic performance is then assembled. Malignant tumors are completely eradicated without relapse via intravenous administration of low-dose Pt/N-CD@TiO 2− x under ultrasound irradiation. This work substantiates the great potential of biocompatible, GSH-responsive p-n junctions as next-generation sonosensitizers via p-n junction-enhanced ROS generation and metal ion oxidation of intracellular GSH.
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高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Yutong Dai,Qingman Li,Shurong Zhang,Shan Shi,Yang Li,Xudong Zhao,Liping Zhou,Xin Wang,Yijian Zhu,Wei Li
Efficient accumulation and on-demand intracellular drug release in the desired site are a crucial issue in developing ideal drug delivery systems (DDSs). Glutathione (GSH)/pH dual-bioresponsive degradable Nanosponges were developed based on β-CD-appended hyper-cross-linked polymer by one-pot polymerization of acryloyl-6- ethylenediamine-6-deoxy-β-Cyclodextrin (β-CD-NH-ACy), acrylic acid (AA) and N , N -bis(acryloyl)- cystamine (BACy) as cross-linker to deliver doxorubcin (DOX) and investigated for GSH/pH triggered DOX release, in which the massive carboxyl and amino groups, and disulfide bonds were used as pH and GSH bioresponsive fragments, respectively. In the proposed DDSs, DOX was readily incorporated into the three dimensional networks of the Nanosponges either as inclusion complexes or as non-inclusion complexes, with a high drug loading capacity of 22.6%. In vitro release studies suggested that the Nanosponges exhibited GSH/pH triggered disintegration and drug release performance, in which DOX release was significantly accelerated in acidic (pH5.0) and cytosolic reduction (10 mM GSH) conditions, with ~77.0% of DOX release. The morphology changes of DOX@Nanosponges in releasing media (pH5.0, 10 mM GSH) were further studied by TEM . Confocal microscopy observation demonstrated that DOX was delivered and released into cytoplasm and nucleus of A549 cells in 7 h incubation with DOX@Nanosponges. MTT assays manifested that the Nanosponges exhibited low cytotoxicity up to a concentration of 1000 μg/mL and DOX@Nanosponges had high anti-tumor activity. These findings demonstrated that the dual-bioresponsive Nanosponges may function as a promising platform for targeted delivery and intracellular drug controlled release in tumor therapy.
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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.
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高影响因子
ADVANCED MATERIALS
·
2023
·
IF 29.4
Suleixin Yang,Yi Wu,Wenzhao Zhong,Ruie Chen,Meilin Wang,Meiwan Chen
Ferroptosis-related cancer therapy is limited by insufficient Fe 2+ /Fe 3+ redox pair and hydrogen peroxide (H 2 O 2 ) for producing lethal hydroxyl radicals (•OH). Although exogenous iron or ROS-producing drugs can enhance ferroptosis, exploiting endogenous iron (labile iron pool, LIP) stored in ferritin and promoting ROS generation may be safer. Herein, a metal/drug-free nanomedicine was developed for responsive LIP release and H 2 O 2 generation on the mitochondria membranes, amplifying hydroxyl radical production to enhance ferroptosis-mediated anti-tumor effects. A GSH/pH dual activatable fluorinated and crosslinked polyethyleneimine with dialdehyde polyethylene glycol layer nanocomplex loaded with MTS-KR-SOD (Mitochondria-targeting-sequence-KillerRed-Superoxide Dismutase) and CRISPR/Cas9-CA IX (Carbonic anhydrase IX) plasmids (FP@MC) were developed for enhanced ferroptosis through endogenous iron de-hijacking and in situ ROS amplification. Two plasmids were constructed to knock down carbonic anhydrase IX and translate KillerRed-SuperOxide Dismutase recombinant protein specifically on mitochondria membranes, respectively. The CA IX knockdown acidified the intracellular environment, leading the release of LIP from ferritin as a “flare” to initiate endogenous chemodynamic therapy. Meanwhile, MTS-KR-SOD generated H 2 O 2 when irradiated by a 590 nm laser to assist chemodynamic therapy, leading to ROS amplification for mitochondria damage and lipid peroxide accumulation. The combined therapeutic effects aggravated cancer ferroptosis and suppressed tumor growth, providing a new paradigm for amplifying ROS and iron ions to promote ferroptosis-related cancer therapy. This article is protected by copyright. All rights reserved
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2024
·
IF 4.3
Xiluan Yan,Shiyun Cheng,Yipi Xiao,Shuangbin Wu,Hongyi Mu,Zhiying Shi,Liang Guo,Fanrong Ai,Xiangjuan Zheng
Metal-organic gels (MOGs) are a type of metal-organic colloid material with a large specific surface area, loose porous structure, and open metal active sites. In this work, FeNi-MOGs were synthesized by the simple one-step static method, using Fe(III) and Ni(II) as the central metal ions and terephthalic acid as the organic ligand. The prepared FeNi-MOGs could effectively catalyze the chemiluminescence of luminol without the involvement of H 2 O 2 , which exhibited good catalytic activity. Then, the multifunctional detected platform was constructed for the detection of GSH and Hg 2+ , based on the antioxidant capacity of GSH, and the strong affinity between mercury ion (Hg 2+ ) and GSH which inactivated the antioxidant capacity of GSH. The experimental limits of detection (LOD) for GSH and Hg 2+ were 76 nM and 210 nM, and the detection ranges were 2–100 μM and 8–4000 μM, respectively. The as-proposed sensor had good performance in both detection limit and detection range of GSH and Hg 2+ , which fully met the needs of daily life. Surprisingly, the sensor had low detection limits and an extremely wide detection range for Hg 2+ , spanning five orders of magnitude. Furthermore, the detection of mercury ions in actual lake water and GSH in human serum showed good results, with recovery rates ranging from 90.10 % to 105.37 %, which proved that the method was accurate and reliable. The as-proposed sensor had great potential as the platform for GSH and Hg 2+ detection applications.
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PubMed
高影响因子
TALANTA
·
2017
·
IF 4.162
Liping Zhang,Bo Ling,Lun Wang,Hongqi Chen
An upconversion luminescence method was developed for the determination of glutathione (GSH), L -cysteine (Cys) or L -ascorbic acid (AA) based on redox reaction . We synthesized poly(acrylic acid) (PAA)-modified Mn 2+ -doped NaYF 4 :Yb,Tm upconversion nanoparticles (UCNPs), and the luminescence of these UCNPs was effectively quenched due to their carboxyl groups coordinating with Fe 3+ to form a UCNPs/Fe 3+ system. GSH, Cys or AA reduced Fe 3+ to Fe 2+ , which induced the luminescence recovery of the UCNPs. Under the optimized conditions, wide linear concentration ranges from 0.25-300 μM for GSH, 0.5–875 μM for Cys and 0.5–350 μM for AA were found, and the detection limits (3 S/K) were 0.2 μM, 0.5 μM and 0.2 μM, respectively. Thus, the UCNPs/Fe 3+ system was successfully applied for sensing GSH, Cys or AA.
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaochun Zheng,Weiwei Kang,Yarong Jin,Xin Zhang,Wenxuan Wang,Dongsheng Li,Shutong Wu,Lin Chen,Shichao Meng,Rong Dai,Ziliang Zheng,Ruiping Zhang
Rheumatoid arthritis (RA) is currently one of the most common systemic autoimmune disorders, with no clinically effective theranostics. Therapeutic manipulation of the gasotransmitter hydrogen sulfide (H 2 S) has exhibited promising potential as an innovative strategy in RA, whereas limited with non-targeting, low solubility, and systemic toxicity. In this work, based on the physicochemical and structural advantages of stimulus-responsive nanotechnology, we develop multifunctional glutathione (GSH)-responsive H 2 S nanogenerators (BDMA NGs), achieving activatable precise second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) bimodal imaging-guided gas/chemotherapy synergistic therapy. Contributed to the suitable size and excellent biocompatibility, the BDMA NGs accumulate passively in the RA region and then feature a responsive deformation reaction with GSH to release functional small molecules: H 2 S and methotrexate (MTX). The H 2 S undergoes a mineralization process with Ag + ions in situ, resulting in the rapid formation of Ag 2 S to “turn on” the NIR-II FL/PA signals. Remarkably, the effective generation of H 2 S downregulates hypoxia-inducible factor-1 α (HIF-1 α ) and promotes nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, thereby restoring homeostasis in the RA microenvironment and facilitating the reprogramming of pro-inflammatory macrophages (M1) into anti-inflammatory phenotype (M2). Moreover, the controlled release of MTX, clinically approved drug for RA, synergistically promotes repolarization to further suppress local inflammation. Overall, the H 2 S-based nanogenerators BDMA NGs present a sophisticated and versatile strategy for implementing stimuli-responsive imaging and M1-to-M2 repolarization, demonstrating significant potential in the theranostics of RA and clinical transformation.
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Hongkun Li,Qianqian Cai,Yangyang Guan,Zhikang Li,Guifen Jie,Hong Zhou
A multimode sensing and imaging platform based on surface modification strategy of Ru(bpy) 3 2+ doped SiO 2 nanoparticles (RuSiO 2 NPs) was constructed for versatile detection of glutathione (GSH). RuSiO 2 NPs as the luminophore models had outstanding fluorescence (FL) and electrochemiluminescence (ECL) signals. Furthermore, its FL signal could be captured by electrophoresis analyzer, and the ECL signal could be imaged with mobile phone to achieve visualization. So, a unique and convenient multi-mode sensing and imaging platform could be developed based on RuSiO 2 NPs. SiO 2 NPs could realize enrichment of Ru(bpy) 3 2+ based on the nanoconfined effect to achieve signal amplification, and its surface was rich with abundant hydroxyl functional groups, which offered a channel for surface modification. Sulfhydryl modification on the RuSiO 2 NPs was realized by using silane coupling agent, and KMnO 4 was used to in situ generate MnO 2 shell on the surface of RuSiO 2 NPs for quenching its ECL, FL, and colorimetric (CL) signals based on resonance energy transfer (RET). Target GSH could reduce MnO 2 shell to realize recovery of all signals, thus achieving the label-free multimode detection of GSH. Therefore, this work developed a multimode sensing and imaging platform without signal labels or layer-by-layer assembly of electrodes, which had the advantages of simple steps, low cost, and high detection accuracy, showing important application potential in the field of bioanalysis.
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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.
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PubMed
高影响因子
SCIENTIA HORTICULTURAE
·
2024
·
IF 3.9
Xinping Wu,Qiuying Li,Yang Yi,Limei Wang,Wenfu Hou,Youwei Ai,Hongxun Wang,Ting Min
The quality of fresh-cut Chinese water chestnuts (CWCs) rapidly deteriorates with prolonged storage time, thus affecting its commercial value. This study aimed to investigate the effect of cinnamaldehyde (CA) treatment on the quality of fresh-cut CWCs and its mechanism of action. CA treatment maintained good appearance and higher total soluble solids content (TSS) of fresh-cut CWCs and also significantly inhibited microbial proliferation, respiration, phenylalanine ammonia-lyase activity (PAL) and enzymatic browning substance content. Moreover, CA treatment increased the antioxidant capacity and defense function-related enzyme activities (PPO and POD) of fresh-cut CWCs, and suppressed ·OH production rate and MDA content. Meanwhile, CA treatment significantly increased the content of antioxidant compounds and enzyme activities of the AsA-GSH cycle system. In conclusion, CA can inhibit surface discoloration of fresh-cut CWCs and extend their shelf life, thus increasing their commercial value.
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高影响因子
危险品化学品经营许可证（带存储）