Nano Research
·
2020
·Vol. 13
·期 1
·160-172
·
IF 8.183
Zhang Amin,Zhang Qian,Alfranca Gabriel,Pan Shaojun,Huang Zhicheng,Cheng Jin,Ma Qiang,Song Jie,Pan Yunxiang,Ni Jian,Ma Lijun,Cui Daxiang
Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment. In this regard, we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic. The multifunctional probes consisted of a gold/platinum star-shaped core (Au/Pt star) conjugated with a GSH-sensitive disulfide bond (S–S), a targeting ligand (rHSA-FA), a near-infrared fluorophore (IR780) and glucose oxidase (GO x ). When systemically administered in a xenografted murine model, the probes specifically targeted the tumor sites. As the disulfide linker was cleaved by intracellular GSH, the IR780 molecules could be released for photo-thermal therapy & photodynamic therapy (PTT&PDT) and imaging. Subsequently, the Pt nanolayer of the Au/Pt star and the GO x formed a sequential catalytic system: GO x effectively catalyzed intracellular glucose by consuming oxygen to generate H 2 O 2 and enhance the local acidity, and the Pt layer exhibited peroxidase-like property to catalyze H 2 O 2 producing toxic ·OH for tumor oxidative damage. Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release, real-time imaging ability, and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features, which provides a potential strategy for effective tumor theragnostic.
研究领域:
癌症治疗
·
生物化学
·
纳米医学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2024
·
IF 3.7
Di Zhang,Wanyu Wei,Tianxiang Xie,Xue Zhou,Xu He,Jie Qiao,Rui Guo,Gang Jin,Ningbo Li
In this study, the mesoporous Fe3O4 nanodrug carriers containing disulfide bonds (CHO-SMNPs) were successfully synthesized and characterized. Doxorubicin (DOX) was loaded onto the CHO-SMNPs as a model drug and gatekeeper through the formation of imine bonds with the aldehyde groups on the surface of the mesoporous materials. This drug carrier demonstrates effective drug release triggered by pH, glutathione (GSH), and near-infrared (NIR) light, along with satisfactory photothermal conversion efficiency under NIR irradiation at 808 nm. Furthermore, CHO-SMNPs exhibit excellent blood compatibility and biodegradability. They also show good biocompatibility and efficient cellular uptake in HeLa and MCF-7 cancer cells. Most importantly, the CHO-SMNPs/DOX has shown significant effectiveness in killing both HeLa and MCF-7 cancer cells. Consequently, CHO-SMNPs/DOX presents substantial potential as a magnetic-targeted, pH/GSH/NIR triple-triggered drug delivery system for synergistic chemo-photothermal therapy in tumor treatment.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 32
·22367-22374
·
IF 3.9
Datian Fu,Yan Wang,Kaiwen Lin,Liangjiu Huang,Jin Xu,Haimei Wu
Although disrupted redox homeostasis has emerged as a promising approach for tumor therapy, most existing photosensitizers are not able to simultaneously improve the reactive oxygen species level and reduce the glutathione (GSH) level. Therefore, designing photosensitizers that can achieve these two aspects of this goal is still urgent and challenging. In this work, an organic activatable near-infrared (NIR) photosensitizer, CyI-S-diCF3, is developed for GSH depletion-assisted enhanced photodynamic therapy. CyI-S-diCF3, composed of an iodinated heptamethine cyanine skeleton linked with a recognition unit of 3,5-bis(trifluoromethyl)benzenethiol, can specifically react with GSH by nucleophilic substitution, resulting in intracellular GSH depletion and redox imbalance. Moreover, the activated photosensitizer can produce abundant singlet oxygen (1O2) under NIR light irradiation, further heightening the cellular oxidative stress. By this unique nature, CyI-S-diCF3 exhibits excellent toxicity to cancer cells, followed by inducing earlier apoptosis. Thus, our study may propose a new strategy to design an activatable photosensitizer for breaking the redox homeostasis in tumor cells.
研究领域:
生物医学工程
·
药学
·
癌症研究
·
化学生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2023
·
IF 3.9
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
The resistance of cancer cells to anticancer drugs has been recognized as one of the main reasons for chemotherapy failure. Multidrug combination therapy is one of the most effective ways to solve this problem. Therefore, in this article, we designed and synthesized a pH/GSH dual-responsive camptothecin/doxorubicin (CPT/DOX) dual pro-drug synergistic treatment system with the aim of overcoming the resistance of non-small cell lung cancer A549/ADR cells to DOX. The pro-drug cRGD-PEOz-S-S-CPT (cPzT) was obtained by linking CPT to poly(2-ethyl-2-oxazoline) (PEOz) with endosomal escape properties through a GSH-responsive disulfide bond and modifying it with the targeted peptide cRGD. The pro-drug mPEG–NH–N=C-DOX (mPX) was synthesized by attaching DOX to polyethylene glycol (PEG) through acid-sensitive hydrazone bonds. The dual pro-drug micelles cPzT/mPX configured according to the CPT/DOX mass ratio of 3:1 showed a strong synergistic therapeutic effect at IC50 with a combined therapy index CI = 0.49, far less than 1. Moreover, with the further improvement of the inhibition rate, the 3:1 ratio showed a stronger synergistic therapeutic effect than other ratios. The cPzT/mPX micelles not only had better targeted uptake ability but also showed a better therapeutic effect in both 2D and 3D tumor suppression assays relative to free CPT/DOX and significantly enhanced the penetration ability into solid tumors. In addition, the results of confocal laser scanning microscopy (CLSM) showed that cPzT/mPX could effectively overcome the resistance of A549/ADR cells to DOX by delivering DOX into the nucleus to exert its effect. Thus, this dual pro-drug synergistic therapy system combining targeting and endosomal escape ability provides a possible strategy to overcome tumor drug resistance.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Yujia Luo,Fang Zheng,Yuanyuan Gao,Wenyu Chen,Xinrui Xue,Chujie Xiao,Kun Wei
Chemodynamic therapy (CDT) generating hydroxyl radicals (•OH) by utilizing metal ions reacting with hydrogen peroxide (H2O2) is a highly encouraging strategy for cancer treatment. However, highly expressed GSH in tumor cells severely limits the efficacy of CDT, and CDT alone is also not sufficient to produce excellent antitumor efficiency. Herein, a dual GSH depletion nanosystem (MnO2@PDA@PEG@DOX) was designed and synthesized to achieve synergistic cancer treatment under ultrasound (US) irritation. To achieve an acidic response, dopamine (DA) was loaded onto manganese dioxide, and the water solubility and stability were greatly improved after PEG modification; finally, the loading of doxorubicin (DOX) achieved the combinational therapy. When the nanoparticles arrived at the tumor site, the acidic and high expression of GSH in the tumor microenvironment prompted the degrading of the nanosystem, followed by the release of MnO2 and DOX. The released MnO2 can react with intracellular GSH to produce Mn2+, which realizes chemodynamic therapy by catalyzing H2O2 to generate highly toxic hydroxyl radicals (•OH) at the tumor site; also, the depletion of GSH will significantly promote the level of •OH, improving the efficiency of CDT simultaneously. Moreover, the release of DOX could be boosted by US irradiation, thus enhancing the effect of chemotherapy on DOX and achieving sonodynamic therapy (SDT). Therefore, strategies to enhance CDT efficiency by dual GSH depletion and combining chemotherapy and sonodynamic therapy modalities can provide more ideas and approaches for combination therapy in cancer treatment.
研究领域:
纳米医学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2024
·
IF 2.7
Yaqi Xiao,Zhi Cai,Ying Yi,Yihua Yin,Weiquan Cai,Guanghua He,Jingli Zhang,Wenjin Xu,Yaru Li
Cationic photosensitizers have higher photodynamic antibacterial activity compared with anionic photosensitizers, and with low toxicity and no drug resistance. However, their poor photostability and low utilization rate limit their practical applications. Herein, a new strategy for the construction of a GSH-responsive antibacterial nanogel system is developed via the electrostatic interaction between methylene blue (MB) and sulfonated sodium alginate (HSSA) to self-assemble into nanoparticles followed by sulfhydryl cross-linking in an aqueous solution. The photobleaching of MB can be inhibited due to the self-aggregation-caused quenching (ACQ) effect, but the photodynamic activity can be restored by breaking the disulfide-crosslinking bonds in the nanogel in response to 10 mM GSH. In vitro antibacterial tests prove that the system has antibacterial activity beyond anionic photosensitizers. Antibacterial studies on plants show that the system has targeted antibacterial activity on infected plants and good wettability, retention, and adhesion to plant leaves. Safety evaluation shows that the system has no obvious toxic effect on plants. Therefore, this study provides a new approach to the discovery of novel photodynamic bactericides.
研究领域:
生物材料学
·
微生物学
·
植物病理学
✓ 已验证
产品关联
DOI
高影响因子
POWDER TECHNOLOGY
·
2025
·
IF 4.6
Menglu An,Weiying Wang,Jingguo Li,Shaokui Cao,Yingliang Liu,Jun Shi
MnO 2 nanosheets have attracted extensive attention in the field of photothermal therapy due to their excellent pH/glutathione (GSH) responsiveness. In this study, MoS 2 @gold nanorods (AuNRs)/polydopamine (PDA)@MnO 2 (400–500 nm) nanocomposites with controllable drug release property were prepared by covering MnO 2 nanosheets around near-infrared (NIR) responsive MoS 2 @AuNRs (100–200 nm) via in-situ redox reaction. The large surface area and strong negative charge of MnO 2 nanosheets ensured that MoS 2 @AuNRs/PDA@MnO 2 had a high loading efficiency of 92.44 % for doxorubicin hydrochloride (DOX). MoS 2 @AuNRs/PDA@MnO 2 revealed significant NIR/pH/GSH triple-responsive drug release properties owing to the synergistically enhanced NIR photothermal-response of MoS 2 @AuNRs (61.10 % of photothermal conversion efficiency) and the reaction between MnO 2 and GSH in weakly acidic media. In addition, in vitro cell viability results confirmed that MoS 2 @AuNRs/PDA@MnO 2 could efficiently kill tumor cells under the dual action of acidic media and NIR laser. This study develops a novel nanocarrier with NIR/pH/GSH triple-responsive drug delivery capability, which has broad applications in photothermal therapy and intelligent drug delivery.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤治疗
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Mingya Wang,Shengling Li,Junli Shi,Yongzheng Liu,Duanlin Cao,Linxiu Zhao
A novel, highly sensitive “on-off-on” fluorescent probe ( E )- N ’-((1 H -imidazol-2-yl) methylene) -4-(5, 5-difluoro-1, 3, 7, 9-tetramethyl-5 H -4 λ 4 ,5 λ 4 -dipyrrolo [1, 2- c :2′, 1′- f ] [1,3,2] diazaborinin-10-yl) benzohydrazide ( BDB ) was developed in this study, and its structural and spectral properties were characterized by 13 C NMR, 1 H NMR, X-ray, ESI-MS, ultraviolet and fluorescence photometry. BDB could specifically and efficiently identify Cu 2+ among many other metal ions with a fluorescence quenching efficiency of 92.7% and a recognition limit of 0.65 μM in CH 3 CN/HEPES (7:3, v/v, pH = 7.23) buffer. The energy difference between BDB and BDB -Cu 2+ complex was calculated by DFT. The BDB -Cu 2+ complex could continuously identify GSH in the same system and show an obvious fluorescence enhancement response with a recovery efficiency of approximately 91% and a low recognition limit of 0.02 μM, which is significantly lower than the physiological concentration of GSH in living cells. The applicability of BDB is verified by the strip test. BDB can also be used to detect GSH in HeLa cells, which expand the application of fluorescent chemical sensors in biology.
研究领域:
分析化学
·
生物化学
·
材料科学
·
生物成像
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2024
·
IF 4
He Mei,Jingcheng Huang,Guixin Wang,Kun Chen,Huili Wang,Xuedong Wang,Wenwei Wang
Herein, we engineered a novel pH-responsive ratiometric assay by virtue of the composite system of Ce 3+ -enhanced glutathione-encapsulated copper nanoclusters (GSH-CuNCs-Ce 3+ ) and N-doped carbon quantum dots (N-CQDs). The GSH-CuNCs-Ce 3+ and N-CQDs were fabricated using one-pot chemical reduction and hydrothermal approaches, respectively, and their morphologies as well as physical and chemical properties were testified in detail by a series of characterization techniques. At 350 nm excitation wavelength, the GSH-CuNCs-Ce 3+ /N-CQDs system (GCC-NC) featured the 440/650 nm dual-emitting property. The ratios of fluorescence intensities (F 650 /F 440 ) demonstrated a strong pH-dependence from 3.0 to 5.0 with a coefficient of determination of 0.9982. Consequently, the GCC-NC system was feasible for constructing a pH-responsive dual-emitting fluoroprobe. Based on the catalytic effect of acetylcholinesterase on acetylcholine to yield acetic acid and further trigger varying solution pH, the as-constructed GCC-NC fluoroprobe was satisfactorily applied for detecting malathion . Under optimized conditions, the newly developed GCC-NC fluoroprobe supplied a wider linear range (0.25–200 μM), lower detection limit (0.075 μM), satisfactory recoveries (96.3–106.2%) and higher precision for malathion in several kinds of fruit juice samples. The fortified experiments by malathion’s structural analogues and metal ions provided compelling evidence that this fluoroprobe had strong anti-interference capacity and high specificity for malathion. These findings render us to believe that the as-constructed pH-responsive dual-emitting fluoroprobe holds great promise in trace malathion assay in food matrices.
研究领域:
分析化学
·
食品安全
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 32
·16738-16754
·
IF 6.895
Weidong Fei,Danfei Chen,Hongxia Tang,Chaoqun Li,Weizeng Zheng,Fengying Chen,Qianqian Song,Yunchun Zhao,Yu Zou,Caihong Zheng
Ferroptosis, a cell death path induced by the generation of reactive oxygen species (ROS), will cause the accumulation of lipid peroxides (PL-PUFA-OOH) and achieve potent tumor-regression. However, glutathione (GSH)-dependent glutathione peroxidase 4 (GPx4) can reduce PL-PUFA-OOH and antagonize the ferroptosis inducing effect of ROS. Herein, folate-PEG modified dihydroartemisinin (DHA) loaded manganese doped mesoporous silica nanoparticles (described as nanomissiles) were constructed for integrating the effect of GSH exhaustion and ROS generation. After endocytosis by tumor cells, intracellular GSH triggered the degradation of nanomissiles, which allowed the simultaneous release of DHA and Fenton catalytic Mn2+ due to the redox reaction between the manganese–oxygen bonds and GSH. The degradation would lead to GSH exhaustion, activation of Mn2+-based magnetic resonance imaging (MRI), and DHA-driven ˙OH generation. The GSH-free environment inhibited the activity of GPx4 and enhanced the accumulation of PL-PUFA-OOH oxidized by ˙OH. Furthermore, the cooperative effects suppressed tumor metastasis by destroying the structure of polyunsaturated fatty acids in the cell membranes and showed potent antitumor activity. This innovative ferroptotic therapy integrating the GSH exhaustion and ROS generation will be a promising strategy for cancer therapy.
研究领域:
纳米技术
·
癌症研究
·
磁共振成像
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NanoImpact
·
2021
·
IF 5.316
Wanjun Zhang,Jinling Gao,Lin Lu,Tsendmaa Bold,Xin Li,Shuo Wang,Zhishang Chang,Jing Chen,Xiao Kong,Yuxin Zheng,Mingliang Zhang,Jinglong Tang
Glutathione (GSH) and glutathione-S-transferases (GSTs) are two frontlines of cellular defense against both acute and chronic toxicity of xenobiotics-induced oxidative stress. The contribution of GSH and GST enzymes to signaling pathways and the regulation of GSH homeostasis play a central role in the detoxification of numerous environmental toxins and impurities. Iron oxide nanoparticles stemmed from traffic exhaust, steel manufacturing, or welding as a potential environmental pollution can lead to adverse respiratory outcomes and aggravate the risk of chronic health conditions via persistent oxidative stress. In this work, two kinds of acute exposure experiments of iron oxide (Fe 2 O 3 and Fe 3 O 4 ) nanoparticles in cells and in vivo were conducted to evaluate the GSH levels and GST activity. Our current research presented Fe 3 O 4 nanoparticles at lower concentrations (≤100 μg/ml) seem to be more toxic to the human bronchial epithelial cells as their consumption of GSH and decrease of GST activity. The catalysis activity of Fe 3 O 4 nanoparticles per se may contribute to the intracellular GSH consumption along with inhibition of glutathione-S-transferase class mu 1 and P (GSTM1 and GSTP1) active site and expression decrease of GSTM1 and GSTP1. Accordingly, the GSH consumption and decrease in GST activity directed to the further lipid peroxidation regarded as an earlier marker for toxicity evaluation of iron oxide nanoparticles, and relevant intervention may be effective for prevention of respiratory exposure induced damage from iron oxide nanoparticles.
研究领域:
毒理学
·
纳米技术
·
细胞生物学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Zhao Yulan,Wu Yang,Xu Quan,Liu Yi,Song Zhiyong,Han Heyou
Reactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H 2 O 2 ) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO 2 @Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO 2 ) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H 2 O 2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO 2 @Dex into biofilms, while CaO 2 generated a substantial amount of H 2 O 2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H 2 O 2 into hydroxyl radicals (•OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO 2 @Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
传染病学
✓ 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）