Regenerative Biomaterials
·
2016
·Vol. 3
·期 5
·299-307
·
IF 0
Sun Hong-Ji,Wang Yan,Hao Tong,Wang Chang-Yong,Wang Qi-Yu,Jiang Xiao-Xia
Glutathione (GSH) depletion has been an important contributor to the dysfunction of dopamine neurons. Polyamidoamine-GSH (PAMAM-GSH) was synthesized and the delivery effect of GSH into PC12 cells was tested. MTT assessment for cytotoxicity and reactive oxygen species (ROS) as well as nitrite oxide (NO) and intracelluar superoxide dismutase (SOD) detection for antioxidative ability were performed. Furthermore, the antiapoptotic ability was analysed by assessing caspase-3, JNK1/2 and Erk1/2 expression. Our data indicated that PAMAM-GSH is an effective agent to replenish GSH into PC12 cells. PAMAM-GSH developed its antioxidative and protective ability for 1-methyl-4-phenylpyridinium (MPP)-induced PC12 cells by reducing the intracellular levels of ROS and SOD activity as well as decreasing the release of NO. Meanwhile, PAMAM-GSH could inhibit caspase-3 activation and might show its antiapoptotic ability to MPP-induced PC12 cells through JNK2/Erk1/2 pathway. In summary, these studies suggest that PAMAM-GSH conjugate has an intrinsic ability to penetrate PC12 cells and deliver GSH into these cells which may provide a new strategy for clinical applications in the treatment of Parkinson’s disease.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
疾病模型
✓ 已验证
产品关联
DOI
PubMed
RSC Advances
·
2015
·Vol. 5
·期 73
·59056-59061
·
IF 3.84
Lun Song,Haiyu Tian,Xiaoliang Pei,Ziyou Zhang,Weibing Zhang,Junhong Qian
Two water-soluble colorimetric and turn-on fluorescent probes STP1–2 were rationally designed and synthesized for selective recognition of GSH. Both probes are colorless 4-thioether-1,8-naphthalimide derivatives, which are almost non-fluorescent due to the photoinduced electron transfer from the fluorophore to the 4-nitrobenzene. Upon addition of GSH to STP1/STP2–CTAB solution, obvious spectral responses were observed: the absorption peak shifted from 345 nm to 390 nm companied with ∼90-fold fluorescence enhancement at 487 nm. A good linear relationship between the fluorescence intensity and GSH concentration was obtained, and the detection limit of GSH was estimated to be 8.40 × 10−8 mol L−1. The experimental results imply that both probes could be applied in fluorescent imaging of GSH within living cells and in the detection of mercapto-containing proteins as well.
研究领域:
生物化学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 10
·2443
·
IF 5.4
Xinqiang Liang,Mekhrdod S. Kurboniyon,Yuanhan Zou,Kezong Luo,Shuhong Fang,Pengle Xia,Shufang Ning,Litu Zhang,Chen Wang
Traditional treatment methods for tumors are inefficient and have severe side effects. At present, new therapeutic methods such as phototherapy, chemodynamic therapy, and gasodynamic therapy have been innovatively developed. High concentrations of hydrogen sulfide (H2S) gas exhibit cancer-suppressive effects. Herein, a Prussian blue-loaded tetra-sulfide modified dendritic mesoporous organosilica (PB@DMOS) was rationally constructed with glutathione (GSH)-triggered/photothermal-enhanced H2S signaling molecule release properties for gas therapy. The as-synthesized nanoplatform confined PB nanoparticles in the mesoporous structure of organosilica silica due to electrostatic adsorption. In the case of a GSH overexpressed tumor microenvironment, H2S gas was controllably released. And the temperature increases due to the photothermal effects of PB nanoparticles, further enhancing H2S release. At the same time, PB nanoparticles with excellent hydrogen peroxide catalytic performance also amplified the efficiency of tumor therapy. Thus, a collective nanoplatform with gas therapy/photothermal therapy/catalytic therapy functionalities shows potential promise in terms of efficient tumor therapy.Keywords:gas therapy;H2S;GSH-triggered;Prussian blue;dendritic mesoporous organosilica
研究领域:
肿瘤学
·
纳米医学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2016
·Vol. 5
·期 2
·274-284
·
IF 3.614
Chaochao Wang,Lichao Liu,Hongliang Cao,Weian Zhang
Ligand-targeted cancer therapeutics has been developed to minimize non-specific cytotoxicity via ligand–drug conjugates during the past few decades. We present here the design and synthesis of a GSH-activated amphiphilic photosensitizer conjugated with galactose (TPP-S-S-Gal) for targeted photodynamic therapy. Furthermore, the galactoside photosensitizer as supramolecular amphiphiles can self-assemble into micelles, which can be applied in integrative cancer treatment with chemotherapy drugs such as camptothecin (CPT) encapsulated in the hydrophobic core of micelles. Upon reaction with free thiol GSH that is relatively abundant in tumor cells, disulfide bond cleavage occurs as well as the active photosensitizer TPP and chemotherapy drug CPT release, which can cause cell apoptosis. The in vitro biological assessment of TPP-S-S-Gal micelles against the A549 cell line was evaluated by MTT assay, flow cytometry and confocal scanning laser microscopy, respectively. According to the MTT assay, TPP-S-S-Gal micelles exhibited low dark toxicity and efficient integrative efficacy of PDT and chemotherapy towards A549 cells after light irradiation.
研究领域:
药理学
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Zhiyuan Liu,Rui Sun,Yaxuan Huang,Fengyun Xu,Nan Li,Wei Zhang,Pengfei Ge,Wenke Zhang
Shikonin (SHK), an active naphthoquinone pigment isolated from the root of Chinese herbal medicine has been proven to have a significant therapeutic effect on breast cancer. However, the poor water solubility as well as the lack of tumor targeting restrict the practice application of SHK molecules as chemotherapeutic agents. Here, SHK drugs were chemically conjugated to polyethylene glycol (PEG) molecules via a disulfide bond (referred to as SHK-SS-PEG) through a facile one-step strategy. The conjugates exhibited an excellent water solubility of 12.96 mM, which is ca. 7807 times as high as that of pure SHK drugs. Noteworthily, the conjugates can self-assemble into spherical micelles with an average particle size of 106 nm, facilitating in vivo delivery as well as the accumulation in tumor tissues based on the enhanced permeability and retention (EPR) effect. Moreover, the disulfide bond enables rapid cleavage of micelles and efficient release of SHK molecules from the conjugates in response to reduced Glutathione (GSH) overexpressed within tumor cells. Thanks to the GSH-responsiveness release of SHK, the conjugate-based micelles (containing 6 μM SHK) resulted in the cell killing rate of 73 % for the MCF-7 breast cancer cells after 48 h incubation, which is 45 % higher than that for the HUVEC normal cells. All these collective beneficial properties make the SHK-SS-PEG conjugate a promising candidate for the treatment of many types of cancers.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2025
·
IF 12.1
Lu Zhang,Huan Shen,Tingting Liu,Bin Li,Xi Chen,Hong Wang,Chenyang He,Yang Liu,Gang Cao,Shuo Yu
Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (H 2 O 2 ) in tumors into highly toxic hydroxyl radicals (•OH) through metal ion-mediated catalysis. However, the effectiveness of CDT is hindered by low catalyst efficiency, insufficient intra-tumor H 2 O 2 level, and excessive glutathione (GSH). In this study, a pH/GSH dual responsive bimetallic nanocatalytic system (CuFeMOF@GOx@Mem) is developed by modifying red blood cell membranes onto glucose oxidase (GOx)-loaded Fe-Cu bimetallic MOFs, enhancing the efficacy of CDT through a triple-enhanced way by H 2 O 2 self-supply, catalysts self-cycling, and GSH self-elimination. Upon accumulation in tumor tissues facilitated by the red blood cell membrane, the GOx initiates a reaction with glucose to generate H 2 O 2 and gluconic acid in situ. Subsequently, the reduced pH triggers the release of Fe 3+ and Cu 2+ from CuFeMOF@GOx@Mem, which is immediately turned into Fe 2+ and Cu + by GSH, activating the Fe 2+ -mediated Fenton reaction. More importantly, Cu + can also act as an accelerator of Fe 3+ /Fe 2+ conversion, meanwhile, the generated Cu 2+ can be further reduced to Cu + by GSH. Consequently, sustained accumulation of H 2 O 2 and Fe 2+ as well as sustained elimination of GSH are achieved simultaneously, providing a unique approach for improving the anti-tumor ability of CDT.
研究领域:
癌症治疗
·
纳米医学
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 6
·3084-3091
·
IF 3.119
Caixue Lin,Hailu He,Yongqi Zhang,Mingyue Xu,Feng Tian,Ling Li,Yingxi Wang
In recent years, the construction of drug carriers that integrate diagnosis and treatment has become a new trend. In this article, a metal–organic framework (Zr-MOF) was synthesized and functionalized using acetaldehyde-modified-cystine (AMC) to form the functional drug carrier Zr-MOF/AMC which could be used to determine the concentration of glutathione (GSH) for cancer diagnosis, and to achieve pH/GSH dual-responsive release of methotrexate (MTX) for cancer therapy. The cleavage of the AMC disulfide bond by GSH generates two fluorescent molecules that produce strongly enhanced fluorescence, and the intensity is proportional to the GSH concentration. The green fluorescence of Zr-MOF/AMC in cancer cells proves that it can be applied in cell imaging to detect abnormal GSH concentrations for early diagnosis. In addition, MTX loaded on the Zr-MOF/AMC is released by the cleavage of the –S–S– and –CN– bonds at the high GSH concentration and low pH in cancer cells. This dual-responsive drug release helps to deliver drugs to cancer cells more precisely. All the experiments suggest that this novel type of pH/GSH dual-responsive Zr-MOF/AMC nanoparticle may serve as a new drug delivery system for cancer diagnosis and treatment.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2024
·Vol. 15
·期 24
·2513-2527
·
IF 4.1
Shuai Yang,Jinhai Xie,Dongdong Wang,Shuangyu Tian,Yaodong Di,Lesan Yan
The distinct variations in the microenvironment between tumor cells and normal cells have facilitated the feasibility of highly specific and efficient drug delivery at tumor sites. This study is based on the elevated levels of glutathione (GSH) and NAD(P)H quinone oxidoreductase (NQO1 enzyme) in the tumor cells, leading to the development of a novel dual-responsive triblock polyurethane (PEG-PTU-SS-PEG) with heightened sensitivity to stimuli. This biodegradable amphiphilic polyurethane contains disulfide bonds responsive to GSH on the main chain and trimethyl locked benzoquinone structures responsive to NQO1 enzyme on the side chains. The polyurethane forms stable micelles through self-assembly and efficiently encapsulates the hydrophobic drug doxorubicin (DOX). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results indicate that both blank and drug-loaded micelles can be effectively disrupted upon addition of GSH or Na2S2O4 (simulating the NQO1 enzyme environment in vitro). Furthermore, the in vitro drug release behavior of drug-loaded micelles, cellular uptake, and cytotoxicity experiments demonstrate that in the presence of GSH and NQO1 enzyme, polyurethane nanomicelles can achieve specific and efficient drug release, enhance cytotoxicity against tumor cells, and maintain excellent biocompatibility. Therefore, this newly developed polyurethane nanodrug delivery system has tremendous potential in tumor therapy, offering specific drug release and efficient treatment.
研究领域:
药物递送
·
生物材料
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
TALANTA
·
2023
·
IF 6.1
Wei Lang,Li-Zhen Chen,Yong Chen,Qian-Yong Cao
Developing efficient photosensitizers which are sensitive to therapeutic tumor signals, but non-toxic to normal cells has always been a tremendous challenge in photodynamic therapy (PDT) process. Herein, a novel copolymer P1 was developed by ring-opening metathesis polymerization (ROMP) with disulfide bond linked ferrocene-norbornene dyad NB-SS-PyFc and the aggregation-induced emission (AIE) fluorephore anchored norbornene NB-TPE , and its nanoparticles (NPs) were obtained by using the amphiphilic Pluronic F-127 as the surfactant via a nanoprecipitation method. The P1 NPs show a weak emission and a low 1 O 2 generation for the quenching effect from the ferrocene moiety to the AIE group. However, the addition of GSH can recover the AIE fluorephore emission and 1 O 2 generation for cleavage the disulfide bond. Importantly, P1 NPs have been used for image-guided cancer cells apoptosis for the GSH activated 1 O 2 generation.
研究领域:
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2020
·
IF 2.69
Xiao Han,Lijuan Wang,Jinsong Du,Jie Dou,Jiang Yuan,Jian Shen
Drug-loaded nanoparticles have been widely used in the field of tumor treatment due to their low side effects and reduced frequency of administration. In this study, keratin-dopamine conjugate was first synthesized by amidation reaction and then formed nanoparticles by self-polymerization of dopamine segment. Keratin-dopamine conjugate nanoparticles (KNPs) exhibited pH and glutathione (GSH) dual responsiveness in the simulated tumor environment. These nanoparticles were able to load anti-cancer drug doxorubicin (DOX) through electrostatic interactions and hydrogen bonds. These drug-loaded KNPs (DKNPs) exhibited controlled drug release in a tumor simulation environment. Meanwhile, DKNPs performed a stronger inhibitory effect on tumor cells compared with human normal tissue cells. Based on the above results, keratin-dopamine conjugate based drug carriers had a broad prospect in the field of cancer treatment.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2021
·Vol. 5
·期 5
·2442-2451
·
IF 6.482
Niu Niu,Huipeng Zhou,Na Yang,Dong Wang,Cong Yu
Polymeric nanoparticles that can respond to a specific tumor microenvironment (TME) show great potential as anticancer agents. In this study, a highly water-soluble polymeric nanoparticle BPP was obtained via atom transfer radical polymerization (ATRP). The strong tendency of self-aggregation of the grafted aromatic benzoperylene facilitated the self-assembly of the polymer into nanoparticles. BPP showed strong excimer emission and could chelate with various metal ions with quenched emission. Cu2+ was then chelated with BPP to form BPC nanoparticles, which were subsequently used as chemodynamic therapy agents. After entering into the cancer cells, BPC could deplete GSH and produce Cu+. Cu+ reacted with intracellular H2O2 and generated toxic hydroxyl radicals (˙OH) via the Fenton-like reaction, which had a fast reaction rate in TME. Because of the high GSH and H2O2 concentrations in tumor cells, BPC NPs exhibited selective cytotoxicity to cancer cells. Additionally, the excimer fluorescence of BPC recovered after entering into the cancer cells, denoting the potential for real time tracking/visualization of drug delivery. The in vivo results also demonstrate that BPC NPs efficiently inhibited tumor growth without obvious systemic toxicity. As a novel Cu2+ chelated polymeric nanomaterial responsive to TME, BPC NPs show excellent potential in chemodynamic cancer therapy.
研究领域:
生物医学工程
·
癌症治疗
·
材料科学
✓ 已验证
DOI
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 7
·2951-2960
·
IF 5.251
Tiangang Yang,Dechao Niu,Jianzhuang Chen,Jianping He,Shaobo Yang,Xiaobo Jia,Jina Hao,Wenru Zhao,Yongsheng Li
Recently, block copolymer micelles have attracted widespread attention due to their controlled biodegradability and excellent loading capability. Unfortunately, the poor in vivo stability and low delivery efficiency of drug-loaded micelles greatly hampered their biomedical applications. Herein, we develop a new kind of biodegradable magnetite/doxorubicin (Fe3O4/DOX) co-loaded PEGylated organosilica micelles (designated as FDPOMs) with both high circulating stability and smart GSH-triggered biodegradability for magnetically targeted magnetic resonance imaging (MRI) and tumor chemotherapy. The FDPOMs are prepared by the self-assembly of biodegradable polycaprolactone-block-poly(glutamic acid) (PCL-b-PGA), a chemotherapeutic DOX drug and Fe3O4 nanoparticles in an oil/water system, subsequent organosilica cross-linking with 3-mercaptopropyltrimethoxysilane (MPTMS) molecules and surface PEGylation. The resultant FDPOMs exhibit excellent dispersity and stability in biological media, remarkable T2-weighted MR imaging capability, unique GSH-responsive release behavior and selective toxicity to tumor cells. The in vivo experiments show that the FDPOMs not only have improved MR tumor imaging capability, but also exhibit high anti-tumor efficacy due to the strong magnetic targeting ability under an external magnetic field. Consequently, the FDPOMs are promising candidates for magnetically targeted MR imaging and imaging-guided tumor chemotherapy.
研究领域:
纳米技术
·
生物材料
·
癌症治疗
·
医学成像
✓ 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）