Inorganic Chemistry Frontiers
·
2023
·Vol. 10
·期 14
·4045-4053
·
IF 7
Zhaoguo Hong,Xin You,Jingjing Zhong,Di Yao,He-Dong Bian,Shulin Zhao,Liangliang Zhang,Hong Liang,Fu-Ping Huang
Chemodynamic therapy (CDT), in which highly toxic hydroxyl radicals (˙OH) could be triggered by a Fenton or Fenton-like reaction to kill cancer cells, has emerged recently. Compared to traditional CDT nanomaterials, herein, an atomically-precise biotinylated Cu(I/II) complex [CuICuIICl2(VBio)]·CH3OH (VBio = deprotonated O-vanillin biotinylhydrazone), denoted VBio-CuICuII, was rationally designed and synthesized successfully. This targeted Fenton-like agent, VBio-CuICuII, is constructed from a hydroxyl radical-producible CuI ion, a CuII center as a GSH depletor for an augmented CDT effect, and a biotin moiety as a cancer-targeting unit. Owing to the obvious cell selectivity discrepancy of biotin towards normal and cancerous cells, VBio-CuICuII was able to preferentially accumulate in tumor cells. Meanwhile, the CuI metal center could be used as a Fenton-like agent to generate ˙OH. Furthermore, the CuII in VBio-CuICuII was available for successive ˙OH production via a CuI/CuII-circulation strategy under a GSH-rich tumor site, thereby improving catalytic efficiency. More importantly, in vivo results further demonstrate that VBio-CuICuII could significantly inhibit tumor growth without obvious damage toward major organs. Therefore, this multiple-identity Fenton-like agent could provide an appreciable reference value for the design of atomically precise CDT agents.
研究领域:
癌症治疗
·
无机化学
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xinmin Zheng,Xiang Li,Guolin Shi,Yidan Zhou,Jinxiao Yan,Hao Zhang,Xiru Liu,Jiangong Zhang,Yu Liu,Liangliang Dai,Hui Yang
The low targeting of immunity regulators & chemotherapy drugs and immune tolerance in the tumor microenvironment significantly hindered the chemo-immunotherapy effect. In this work, an MMP-2/GSH-responsive nanobomb loading Resiquimod (R848) and prodrug Cisplatin (Pt) with hierarchical drug delivery and tumor associated macrophages (TAMs) polarization traits was designed for improved chemo-immunotherapy. The Pt-carrying dendrimers penetrate the depth of tumor tissues under MMP-2 and activate the cytotoxicity of Pt prodrug in response to GSH, causing effective tumor damage and enhancing immunogenicity. Meanwhile, R848 is effectively uptake by TAMs, which were re-educated and then greatly relieved immune resistance. In vitro and in vivo results collectively revealed that the nanosystem could not only overcome the barrier of tumor penetration and the heterogeneity action sites of drugs but also re-educate TAMs and suppress immune evasion via activating extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signal pathway regulated by heparin binding EGF like growth factor ( Hbegf ) gene. The gene silencing or knockout in vitro and in vivo demonstrated that Hbegf could regulate the re-education of TAMs and the progression of tumors.
研究领域:
肿瘤学
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免疫学
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药剂学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Qiuxing Liu,Xin Ding,Xiaoyu Xu,Hualu Lai,Zishan Zeng,Ting Shan,Tao Zhang,Meixu Chen,Yanjuan Huang,Zeqian Huang,Xiuling Dai,Meng Xia,Shengmiao Cui
Tumor cells with innate oxidative stress are more susceptible to exogenous ROS-mediated oxidative damage than normal cells. However, the generated ROS could be scavenged by the overexpressed GSH in cancer cells, thus causing greatly restricted efficiency of ROS-mediated antitumor therapy. Herein, using cinnamaldehyde (CA) as a ROS generator while β-phenethyl isothiocyanate (PEITC) as a GSH scavenger, we designed a tumor-targeted oxidative stress nanoamplifier to elevate intracellular ROS level and synchronously suppress antioxidant systems, for thorough redox imbalance and effective tumor cells killing. First, an amphiphilic acid-sensitive cinnamaldehyde-modified hyaluronic acid conjugates (HA-CA) were synthesized, which could self-assemble into nano-assembly in aqueous media via strong hydrophobic interaction and π-π stacking. Then, aromatic PEITC was appropriately encapsulated into HA-CA nano-assembly to obtain HA-CA/PEITC nanoparticles. Through enhanced permeability retention (EPR) effect and specific CD44 receptor-mediated endocytosis, HA-CA/PEITC nanoparticles could accumulate in tumor tissues and successfully release CA and PEITC under acidic lysosomal environment. Both in vitro and in vivo results showed that the nanoparticles could efficiently boost oxidative stress of tumor cells via generating ROS and depleting GSH, and finally achieve superior antitumor efficacy. This nanoamplifier with good biosafety provides a potential strategy to augment ROS generation and suppress GSH for enhanced oxidation therapy.
研究领域:
纳米技术
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药学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2020
·
IF 4.383
Jinhui Hu,Ting Wang,Lin Zhou,Shaohua Wei
Reduced glutathione (GSH, containing sulfydryl) inside cancer cells strongly consumes reactive oxygen species (ROS) in photodynamic therapy (PDT) process to reduce PDT effect. Thiol-ene click reaction is a classic method to couple sulfydryl and alkene groups. However, little effort was dedicated to developing medicines for GSH depletion based on this reaction. Our research indicated that GSH could effectively couple with docosahexaenoic acid (DHA, as alkene) in the presence of 2,2-dimethoxy-2-phenylacetophenone (DMPA, as photo-initiator) post 665 nm light irradiation through the thiol-ene click reaction. Based on this result, a ROS responsive nanocarrier (denoted as RSV) was used to load photosensitizer (zinc phthalocyanine, ZnPc), DHA and DMPA (denoted as DDRZ NP). Our research demonstrated that DDRZ NP could effectively accumulate at tumor tissue post tail vein injection . After irradiated by 665 nm light at tumor tissue, RSV was broken by ROS to release the encapsulated drugs . After that, the thiol-ene click reaction was initiated to couple GSH and DHA to deplete intracellular GSH. In addition, DDRZ NP destroyed GSH biosynthesis limiting enzyme , γ-glutamylcysteine synthetase (γ-GCS), to inhibit intracellular GSH biosynthesis. Above dual mechanisms, by GSH depletion and biosynthesis inhibition, could effectively guarantee intracellular GSH concentration decreasing to ensure satisfactory PDT cancer treatment outcome.
研究领域:
纳米技术
·
药学
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癌症治疗
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化学生物学
✓ 已验证
产品关联
DOI
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.
研究领域:
纳米技术
·
分析化学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2020
·
IF 3.83
Jinyue Zhang,Mingshi Jin,Yong Il Park,Longyi Jin,Bo Quan
Manganese silicate nanoparticles have recently attracted great attention due to the effectiveness of T 1 -weighted magnetic resonance imaging (MRI) contrast agents (CAs) in the mildly acidic and high glutathione (GSH) conditions of the tumor microenvironment. Herein, ultra-small hollow manganese silicate (UHMS) nanoparticles were prepared via a facile, economical, and eco-friendly method based on a hydrothermal process using small silica nanoparticles as both the silicon source and templates. The nanoparticles showed remarkable biocompatibility and dispersion stability after modification with polyethylene glycol (PEG). Owing to their ultra-high longitudinal relaxation rate (r 1 ) at low pH values and high GSH levels, the [email protected] nanoparticles have performed an excellent pH/GSH-responsive T 1 -weighted MRI. Meanwhile, the nanoparticles showed insignificant cytotoxicity in vitro and in vivo. Therefore, the [email protected] nanoparticles show promise as T 1 -MRI CAs in the tumor microenvironment and may be used to assist in clinical cancer diagnosis.
研究领域:
纳米技术
·
材料科学
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医学成像
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 45
·5803-5809
·
IF 2.378
Xuefang Yang,Mengting Zhang,Yulu Zhang,Ning Wang,Wei Bian,Martin M. F. Choi
Nitrogen and phosphorus co-doped carbon dots (NPCDs) were synthesized by a microwave method, using citric acid monohydrate and diammonium hydrogen phosphate as raw materials. The morphology, structures and elemental compositions of NPCDs were characterized by transmission electron microscopy, X-ray diffractometry, and X-ray photoelectron spectroscopy. It was found that NPCDs show good selectivity to Hg2+ over other metal ions. And the fluorescence of the NPCDs-Hg2+ system can be recovered in the presence of glutathione (GSH). As such, a “turn-off-on” fluorescence probe can be constructed for the detection of Hg2+ and GSH. Under the optimum working conditions, the linear response of NPCDs to Hg2+ was in the range 0.10–30 μM with a detection limit of 9.9 nM. The linear range of GSH was 0.50–32 μM with a limit of detection of 11.2 nM. The proposed method has been successfully applied to the detection of Hg2+ and GSH in various biological samples. What is more, NPCDs have low cytotoxicity verified by the MTT assay. Using NPCDs as a probe, fluorescence images were obtained for HepG2 cells, which indicated that it could monitor the levels of Hg2+ and GSH in biological systems.
研究领域:
分析化学
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材料科学
·
生物化学
·
细胞生物学
✓ 已验证
产品关联
DOI
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
研究领域:
癌症治疗
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基因治疗
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纳米医学
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Saudi Chemical Society
·
2021
·
IF 3.932
Shuhua Cao,Fahui Li,Qian Xu,Meng Yao,Shun Wang,Yunjun Zhou,Xiaotong Cui,Ruolin Man,Kaoxue Li,Xishi Tai
A novel tetranuclear copper complex (TCC) has been successfully synthesized and characterized using high resolution mass spectrometry (HRMS), Fourier transform infrared spectroscopy (FTIR) and X-ray single crystal diffraction technique. TCC was capable of triggering by Glutathione (GSH) to produce Cu (Ⅰ), then the resulted Cu (Ⅰ) further converted the overexpression of endogenous H 2 O 2 into •OH, a highly cytotoxic reactive oxygen species (ROS), thereby killing the cancer cells. TCC showed high cytotoxicity to 4T1, MCF7, HepG2 cancer cells. Interestingly, the cytotoxicity of TCC to non-cancerous cells is much lower than that of cancer cells. Cell cycle experiments demonstrated that TCC was capable of arresting the cancer cell cycle in the G2/M phase. The apoptosis experiments shown that TCC could induce apoptosis rather than necrosis.
研究领域:
无机化学
·
材料科学
·
癌症研究
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生物化学
✓ 已验证
产品关联
DOI
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.
研究领域:
食品科学
·
采后生理学
·
植物生物化学
✓ 已验证
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Jun Hou,Yanbao Zhao,Lei Sun,Xueyan Zou
Hyaluronic acid (HA) is a naturally polysaccharide that has been used for drug delivery, but is limited by low drug loading capacity and drug leakage in circulation. To improve drug delivery efficient, HA modified porous silica (pSiO 2 ) nanocarriers were successfully prepared for drug delivery and combining therapy. pSiO 2 nanocarriers have stable porous structure and high loading capacity, and pSiO 2 /HA nanocarriers would possess advantages of HA-based carriers and pSiO 2 nanoparticles . Herein, pSiO 2 nanocarriers were prepared by two-phase process, followed by embedding Ag 2 S QDs in the pore walls of pSiO 2 carriers, which render the carriers photothermal effect. pSiO 2 nanocarriers have size of 30 nm, large channels, and high loading capacity (29.3 %). To graft HA, a sensitive linker with alkyl amine and disulfide bond was conjugated on the surface of Ag 2 S/pSiO 2 nanocarriers by three-step reaction. After loading doxorubicin (DOX), HA was grafted via sensitive linker onto the surface of Ag 2 S/pSiO 2 carriers via the formation of amide bonds to seal the loaded drugs. The interaction between HA and CD44 confers the carrier targeting ability to cancer cells. HA coating can be degraded by hyaluronidase resulting in the release of internal cargo. The Ag 2 S/pSiO 2 /HA nanocarriers performs responsive drug release and combining photothermal chemotherapy.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2019
·Vol. 15
·期 41
·1903016
·
IF 10.856
Nan Yan,Lin Lin,Caina Xu,Huayu Tian,Xuesi Chen
Developing tumor-responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated–DNA nanodevice, based on the fluorescence nucleic acid probe and polymer-modified MnO 2 nanosheets, for glutathione (GSH)-gated miRNA-21 signal amplification and GSH-activated magnetic resonance (MR) imaging–guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false-positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor-responsive hydroxyl radical ( · OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase-like activity and glucose oxidase–like activity with the performance of O 2 production and glucose consumption. This is the first time to fabricate a tumor-responsive theranostic DNA nanodevice with tumor-specific signal amplification of microRNA and GSH-activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.
研究领域:
生物医学工程
·
纳米技术
·
诊疗学
·
分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）