BIOMACROMOLECULES
·
2023
·
IF 6.2
Yingping Zeng,Guangtao Song,Shufen Zhang,Sufen Li,Tingting Meng,Hong Yuan,Fuqiang Hu
The tumor microenvironment (TME) of breast cancer is hypoxic, which can promote tumor progression, including invasion and metastasis, and limit the efficacy of anti-tumor treatment. Nitric oxide (NO) can dilate blood vessels, effectively alleviate hypoxia, and regulate the TME, which has the potential to improve the anti-tumor therapeutic efficacy. Here, chitosan (CO) and octadecylamine (ODA) were linked by the disulfide bond, and the LinTT1 peptide was linked onto CO–SS–ODA for targeting tumor cells and endothelial cells in tumors. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) was connected to CO. Doxorubicin (DOX) was encapsulated, and GSH hierarchically responsive polymer micelles (TSCO–SS–ODA/DOX) were constructed for the treatment of breast cancer. The micelles had differently responsive drug release in different GSH concentrations. In endothelial cells, the micelles rapidly responded to release NO. In tumor cells, the disulfide bond rapidly broke and released DOX to effectively kill tumor cells. The disulfide bond was not sensitive to GSH concentration in endothelial cells, which had less release of DOX. The killing effect of the micelles to endothelial cells was much lower than that to tumor cells. The cell selective drug release of the drug delivery systems enabled safe and effective treatment of drugs. TSCO–SS–ODA/DOX, which had the excellent ability to target tumors, can alleviate tumor hypoxia, decrease the infiltration of M2 macrophages in tumors, increase the infiltration of M1 macrophages in tumors, and remodel the TME. Notably, TSCO–SS–ODA/DOX can significantly inhibit the growth of the primary tumor and effectively inhibit tumor metastasis. The drug delivery system provided a potential solution for effectively treating breast cancer.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Yumeng Miao,Yun Zheng,Yanzhi Geng,Ling Yang,Na Cao,Yue Dai,Zhifeng Wei
Background: Peroxisome proliferator-activated receptor gamma (PPARγ) has the ability to counter Th17 responses, but the full mechanisms remain elusive. Herein, we aimed to elucidate this process in view of cellular metabolism, especially glutaminolysis. Methods: MTT, CCK-8, Annexin V-FITC/PI staining or trypan blue exclusion assays were used to analyze cytotoxicity. Flow cytometry and Q-PCR assays were applied to determine Th17 responses. The detection of metabolite levels using commercial kits and rate-limiting enzyme expression using western blotting assays was performed to illustrate the metabolic activity. ChIP assays were used to examine H3K4me3 modifications. Mouse models of dextran sulfate sodium (DSS)-induced colitis and house dust mite (HDM)/lipopolysaccharide (LPS)-induced asthma were established to confirm the mechanisms studied in vitro . Results: The PPARγ agonists rosiglitazone and pioglitazone blocked glutaminolysis but not glycolysis under Th17-skewing conditions, as indicated by the detection of intracellular lactate and α-KG and the fluorescence ratios of BCECF-AM. The PPARγ agonists prevented the utilization of glutamine and thus directly limited Th17 responses even when Foxp3 was deficient. The mechanisms were ascribed to restricted conversion of glutamine to glutamate by reducing the expression of the rate-limiting enzyme GLS1, which was confirmed by GLS1 overexpression. Replenishment of α-KG and 2-HG but not succinate weakened the effects of PPARγ agonists, and α-KG-promoted Th17 responses were dampened by siIDH1/2. Inhibition of KDM5 but not KDM4/6 restrained the inhibitory effect of PPARγ agonists on IL-17A expression, and the H3K4me3 level in the promoter and CNS2 region of the il-17 gene locus down-regulated by PPARγ agonists was rescued by 2-HG and GLS1 overexpression. However, the limitation of PPARγ agonists on the mRNA expression of RORγt was unable to be stopped by 2-HG but was attributed to GSH/ROS signals subsequent to GLS1. The exact role of PPARγ was proved by GW9662 or PPARγ knockout, and the mechanisms for PPARγ-inhibited Th17 responses were further confirmed by GLS1 overexpression in vivo . Conclusion: PPARγ agonists repressed Th17 responses by counteracting GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals, which is beneficial for Th17 cell-related immune dysregulation.
研究领域:
免疫学
·
细胞代谢
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2022
·
IF 3.221
Hengquan Zhou,Guiying Li,Lei Guo,Qian Tao,Songmei Ma,Xunyong Liu
pH and GSH dual-responsive nanoparticles with fluorescence detection were successfully prepared from the polydopamine coating on the surface of mesoporous silica via disulfide bonds (MSN-SS-PDA). The average diameter of nanoparticles was about 80–100 nm with a well-ordered mesoporous structure. The outer layer of PDA was about 10.0 nm acting as a pH and GSH sensitive gatekeeper to control drug release. Doxorubicin (DOX) was loaded into mesoporous channels to evaluate the drug loading capacity and controlled release performance. TPE-4OH, an aggregation-induced emission (AIE) luminescence, was adhered to the surface of PDA for detection of drug release in real-time. The drug release from MSN-SS-PDA nanoparticles was enhanced under acidic solutions or high GSH concentrations. The fluorescence intensity decreased gradually with the drug release, which can be used for monitoring of release process. Besides, the nanoparticles exhibited good photothermal conversion capability due to the PDA layer under near-infrared light irradiation at 808 nm. These nanoparticles present a promising future for combination therapy and real-time tracking of the release process.
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2015
·
IF 6.409
Qing Han,Xin Shen,Wanying Zhu,Chunhong Zhu,Xuemin Zhou,Huijun Jiang
A novel magnetic molecularly imprinted sensing film (MMISF) was fabricated for the determination of estradiol (E2) based on magnetic glassy carbon electrode (MGCE) and magnetic molecularly imprinted polymers (MMIPs). The MMIPs were synthesized by in situ polymerization of glutathione (GSH)-functionalized gold (Au)-coated Fe 3 O 4 (Fe 3 O 4 @Au-GSH) nanocomposites and aniline. The MMISF was constructed with MMIPs via a kind of “soft modification” where MMIPs were assembled and immobilized on the surface of MGCE or removed from it by freely installing a magnet into MGCE or not. The E2-MMIPs were obtained by MMIPs recognizing E2 from sample, and the electrochemical detection was carried out after forming the “soft modification” sensing film by putting MGCE into the E2-MMIPs suspension liquid. Afterwards, the “soft modification” MMISF was peeled off from the electrode by removing the magnet from MGCE. The interface of the electrode could be quickly refreshed through simple treatment for the next detection. The structures and morphologies of Fe 3 O 4 @Au-GSH, MMIPs and MMISF were investigated by Fourier transform infrared spectrometer, ultraviolet and visible spectrophotometer, scanning electron microscope and atomic force microscope . In addition, the MMISF was successfully used for detecting E2 in milk powder with good sensitivity, selectivity, reproducibility and efficiency. The linear range of the MMISF for E2 was 0.025–10.0 μmol L −1 with the limit of detection of 2.76 nmol L −1 ( S / N = 3).
研究领域:
分析化学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Fuqiang Shi,Jie Chen,Lesan Yan,Jing Tu
Chemodynamic therapy (CDT), an innovative approach for treating bacterial infections, has garnered significant attention due to its ability to generate hydroxyl radicals (•OH) via Fenton/Fenton-like reactions. However, the effectiveness of CDT is considerably hindered by the limited availability of endogenous hydrogen peroxide (H2O2) and the overexpression of glutathione (GSH) within the infection microenvironment. To address these limitations, a multifunctional nanoplatform with self-supplying H2O2, GSH-depletion properties, and photothermal properties was developed through a straightforward and mild strategy. This platform employs calcium peroxide (CaO2) as the core, coated with silica (SiO2) to enhance stability and further modified with a Cu(II)-doped polydopamine (PDA) layer, forming a core–shell structured CaO2@SiO2@PDA-Cu (CSPC). The Cu(II) released by CSPC, combined with the H2O2 produced from CaO2 degradation, participates in a Fenton-like reaction to generate toxic •OH radicals. Additionally, Cu(II)-mediated redox reactions deplete overexpressed GSH, thereby enhancing CDT efficacy. Upon coordination with Cu(II), the photothermal properties of PDA are significantly enhanced, achieving a photothermal conversion efficiency of up to 43%. The hyperthermia induced by photothermal therapy (PTT) further increases •OH production, augmenting CDT. The CSPC nanomaterials demonstrated outstanding synergistic photothermal bactericidal activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) at 60 μg/mL, achieving complete eradication. Moreover, CSPC eliminated 65.90 ± 3.46% of the S. aureus biofilm under near-infrared (NIR) irradiation. In vivo experiments demonstrated that CSPC treatment effectively eradicated bacteria, with a bacterial survival rate of 6.56 ± 3.28%, and accelerated wound healing, reducing the relative wound size to 7.0 ± 2.6%. Therefore, this study successfully developed versatile nanomaterials that significantly enhance the PTT/CDT dual-mode antibacterial performance.
研究领域:
生物医学工程
·
纳米医学
·
抗菌治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Hao Zhang,Dan Xie,Meng Chen,Qiangqiang Yin,Guangyue Shi,Jialong He,Xiaoyang Yu,Qian Lu,Zhengji Wang,Jing Dong,Liguo Hao
Chemotherapy is a widely used cancer treatment modality, while the complex tumor microenvironment (TME) significantly impedes drug delivery and deep tissue penetration. An MR molecular imaging drug-loaded nanomotor has been developed to achieve deep tumor tissue penetration and imaging-guided drug delivery, enabling combined photothermal and chemotherapeutic treatment of pancreatic cancer. A Janus-type nanomotor (Au@H-MP NMs) was fabricated via magnetron sputtering for application in photothermal therapy. Doxorubicin (DOX) was loaded onto one hemisphere of the nanomotor, achieving combined photothermal and chemotherapeutic treatment. Additionally, the nanomotor exhibits dual responsiveness to pH and glutathione (GSH), facilitating the controlled release of DOX within deep tumor tissues. Studies confirmed the nanomotors excellent biosafety, strong photothermal conversion capability, and effective induction of apoptosis. Tumor tissue penetration was validated through in vitro migration and infiltration assays, while in vivo experiments demonstrated significant tumor suppression and enhanced drug accumulation. Moreover, MR imaging technology enables real-time monitoring of nanomotor dynamics. These findings suggest that the synthesized Janus-type MR molecular imaging nanomotor offers a promising strategy for multimodal treatment of pancreatic cancer with significant clinical potential.
研究领域:
肿瘤学
·
生物医学工程
·
药理学
·
影像医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2020
·Vol. 137
·期 43
·49339
·
IF 2.52
He-Yi Li,Fang-kun Jing,Jun-Feng Hao
In order to reduce the toxic side effects of chemotherapeutic drugs and improve the targeting and efficiency of cancer treatment, the development of drug delivery system has received great attention. In this study, second generation polyglutamic acid dendrimers (G 2 ) are used as basic materials to produce porous nanoparticles through cross link by crosslinkers containing disulfide bonds. The crosslinked products (G 2 ) n have negative electricity and abundant voids, which enable them to adsorb the electronegative anticancer drug DOX. At the same time, in order to transport DOX to the tumor site, we modified FA on DOX and encapsulated it in magnetic mesoporous silica (FA-DOX-MSNs). Therefore, the final nanoparticles (FA-DOX-MSNs/(G 2 ) n ) not only have dual targeting ability to transport DOX to the tumor site, but also have reductive responsiveness that can release drugs responsively in the tumor cells. In addition, it has good biocompatibility and endocytosis ability.
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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yanwen Zhu,Zhaoliang Hu,Yunen Liu,Tingcai Yan,Ling Liu,Yanqun Wang,Bing Bai
Hydrogen sulfide (H 2 S), or dihydrogen sulfane (H 2 S n ), acts as a signal molecule through the beneficial mechanism of persulfidation, known as the post-translational transformation of cysteine residues to persulfides. We previously reported that Glutathione (GSH) could regulate enzyme activity through S-desulfurization or glutathionylation of residues to generate protein-SG or protein-SSG, releasing H 2 S. However, little is known about the mechanisms by which H 2 S n and GSH affect the disulfide bonds . In this study, we provide direct evidences that H 2 S n and GSH modify the sulfhydryl group on Cys272, which forms disulfide bonds in acetylcholinesterase (AChE), to generate Cys-SSH and Cys-SSG, respectively. Glutathionylation of disulfide is a two-step reaction based on nucleophilic substitution, in which the first C S bond is broken, then the S S bond is broken to release H 2 S. H 2 S n and GSH controlled self-breathing motion in enzyme catalysis by disconnecting specific disulfide bonds and modifying cysteine residues, thereby regulating AChE activity. Here, we elucidated H 2 S n and GSH mechanisms on disulfide in the AChE system and proposed a self-breathing control theory induced by H 2 S n and GSH. These theoretical findings shed light on the biological functions of H 2 S n and GSH on sulfhydryl and disulfide bonds and enrich the theory of enzyme activity regulation.
研究领域:
生物化学
·
分子生物学
·
酶学
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Zhongyin Chen,Lihui Wan,Ye Yuan,Ying Kuang,Xiangyu Xu,Tao Liao,Jia Liu,Zi-Qiang Xu,Bingbing Jiang,Cao Li
The purpose of developing novel anticancer drug delivery systems (DDSs) is to efficiently carry and release drugs into cancer cells and minimize side effects. In this work, based on hollow mesoporous silica nanoparticle (HMSN) and the charge-reversal property, a pH/GSH-dual-sensitive DDS named DOX@HMSN–SS-PLL(cit) was reported. HMSN encapsulated DOX with high efficacy and was then covered by the “gatekeeper” β-cyclodextrin (β-CD) through the glutathione (GSH)-sensitive disulfide bond. Thereafter, adamantine-blocked citraconic-anhydride-functionalized poly-l-lysine (PLL(cit)-Ad) was decorated on the surface of the particles via host–guest interaction. The negatively charged carriers were stable in the neutral environment in vivo and could be effectively transported to the tumor site. The surface charge of the nanoparticles could be reversed in the weakly acidic environment, which increased the cellular uptake ability of the carriers by the cancer cells. After cellular internalization, β-CD can be removed by breakage of the disulfide bond in the presence of a high concentration of GSH, leading to DOX release. The preparation process of the carriers was monitored. The charge-reversal capability and the controlled drug-release behavior of the carriers were also investigated. In vitro and in vivo experiments demonstrated the excellent cancer therapy effect with low side effects of the carriers. It is expected that dual-sensitive DOX@HMSN–SS-PLL(cit) could play an important role in cancer therapy.
研究领域:
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2020
·Vol. 49
·期 34
·11851-11858
·
IF 4.174
Shuhua Cao,Xuezhao Li,Yong Gao,Fahui Li,Kaoxue Li,Xuanxuan Cao,Yiwen Dai,Lirong Mao,Shanshan Wang,Xishi Tai
A bimetallic Cu(II) complex as a novel antitumor chemodynamic therapy agent with glutathione (GSH) depletion properties is successfully synthesized and well characterized. In tumor cells, the Cu2+ ions of the complex are reduced to Cu+ ions by GSH and then catalyzed by the overexpressed H2O2 to generate highly cytotoxic hydroxyl radicals (˙OH) that kill cancer cells. The complex is quickly taken up by cancer cells and distributed in multiple organelles including mitochondria and the nucleus. The complex demonstrates good cytotoxicity toward various cancer cell lines. However, its toxicity toward normal cells is significantly lower than that toward cancer cells due to the limited expression of H2O2. In addition, the complex could arrest the cell cycle of the G0/G1 phase, thereby inducing apoptosis rather than necrosis.
研究领域:
化学
·
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 12
·5359-5368
·
IF 5.251
Yadong Liu,Zhanwei Zhou,Yidi Liu,Yanhui Li,Xinzhi Huang,Chenggen Qian,Minjie Sun
Photodynamic therapy (PDT) is a clinically approved cancer treatment approach that relies on the generation of excess reactive oxygen species (ROS) to eradicate tumor cells by inducing oxidative stress. Unfortunately, if the tumor's endogenous glutathione (GSH) is overexpressed, it will eliminate the ROS and restrict the therapeutic efficacy of PDT. Herein, we report a H2O2-activated oxidative stress amplifier (OSA) for enhancing the ROS generation for PDT via GSH scavenging. Cinnamaldehyde (Cin) and chlorin e6 (Ce6) were applied as the GSH scavenger and photosensitizer, respectively, which were assembled with the ROS-responsive amphipathic polymer (DPL) to form DPL@CC micelles as the OSA. In the circulation of blood, the OSA can effectively protect the Cin from albumin binding to retain its GSH depletion ability. Once the OSA reached the tumor site, the high level of H2O2 triggered the degradation of DPL and led to the release of Cin and Ce6. Subsequently, the released Cin reacted with the intracellular GSH by Michael Addition and downregulated the GSH level to about 18.9%, versus untreated cells, to weaken the anti-oxidation ability of tumor cells. Thus, it provided a suitable environment for PDT to obtain an amplifying effect on oxidative stress and superior anti-cancer efficacy of 94% growth inhibition. The preparation of the H2O2-activated oxidative stress amplifier is a convincing strategy for promoting intracellular ROS generation and enhancing the tumor PDT efficacy, which could also augment the clinical application of PDT.
研究领域:
癌症治疗
·
药学
·
生物医学工程
·
化疗
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Nian Liu,Hongsen Liu,Haoran Chen,Gang Wang,Haolin Teng,Yulei Chang
Photodynamic therapy (PDT) is one of the non-invasive and selective treatment methodologies for cancer. However, many highly efficient photosensitizers (PSs) are usually low physiological solubility, limited bioavailability and tending aggregation, impeding the effectiveness of PDT, as well as cancer resistance of PDT further reduce its therapeutic effect. Though some smart delivery systems have been developed, the problem of photosensitizer leakage/release has not been completely solved. Herein, we developed a smart therapeutic nanoplatform based on polyphotosensitizer nanogel as novel nanophotosensitizers and drug carriers. Moreover, by loading of histone deacetylase inhibitors (SAHA), it allows for enhanced synergistic therapy strategy of prostate cancer via inhibiting HIF-1α and VEGF pathways of cancer cells involved in PDT resistance. Our study presents the well-designed nanoplatform of nanogel-Ce6, which could serve as a photodynamic agent without Ce6 molecules release in the responsive environment, offering the potential to encapsulate diverse functional components for smart drug release and imaging-guided combination therapy in vitro and in vivo .
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物医学工程
✓ 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）