Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-11
·
IF 4.703
Li Zihaoran,Wu Xinghan,Wang Wenyu,Gai Chengcheng,Zhang Weifen,Li Wentong,Ding Dejun
Suppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer, which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Owing to its poor water solubility and limited intracellular iron content, it is challenging for further application in antitumor therapy. Herein, we developed ferrous-supply nano-carrier for ART based on tannic acid (TA) and ferrous ion (Fe(II)) coated on the zeolitic imidazolate framework-8 (ZIF) with ART encapsulated (TA-Fe/ART@ZIF) via coordination-driven self-assembly. Drug release experiments showed that ART was not nearly released in pH 7.4, while 59% ART was released in pH 5.0 after 10 h, demonstrating the excellent pH-triggered release. Meanwhile, a high level of intracellular ROS and MDA, accompanied with decreasing GSH and GPX4, displayed a newly developed nano-drug system displayed markedly enhanced ferroptosis. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated higher efficiency of tumor suppression of TA-Fe/ART@ZIF. This work provides a novel approach to enhance the potency of ferroptotic nano-medicine and new directions for TBNC therapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-11
·
IF 4.6
Fengchao Chen,Siya Zhang,Tongtong Yan,Hongquan Wang,Jie Li,Qiang Wang,Danish Subhan,Kun Li
Recently, natural photosensitizers, such as berberine, curcumin, riboflavin, and emodin, have received more and more attention in photodynamic therapy. Tanshinone I (TanI) is extracted from a traditional Chinese herb Danshen, and exhibits many physiological functions including antitumor. TanI is a photoactive phytocompounds, but no work was tried to investigate its potential photodynamic effect. This study evaluated the cytotoxicity induced by the photodynamic effect of TanI. The photochemical reactions of TanI were firstly investigated by laser flash photolysis. Then breast cancer cell line MDA-MB-231 was chosen as a model and the photodynamic effect of TanI on cancer cell was evaluated by MTT assay and flow cytometry. The results showed that TanI could be photoexcited by its UV–Vis absorption light to produce 3 TanI* which was quickly quenched by O 2 . MTT assay showed that the photodynamic effect of TanI resulted in more obvious inhibitive effect on cell survival and cell migration. Besides, the photodynamic effect of TanI could induce cell apoptosis and necrosis, lead to cell cycle arrest in G2, increase intracellular ROS, and decrease the cellular Δψm. It can be concluded that the photodynamic effect of TanI can obviously enhance the cytotoxicity of TanI on MDA-MB-231 cells in vitro, which indicated that TanI might serve as a natural photosensitizer.
研究领域:
药理学
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肿瘤学
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光动力疗法
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Ruo-Fei Bai,Yi-Wei Wang,Shan-Shan Yang,Yu-Hao Zhang,Bo-Hang Zhou,Cong-Wei Zhou,Le Zhou
As part of our continuing research on propiolic acid derivatives, a series of benzyl propiolate derivatives and analogues were designed, synthesized, and investigated for inhibition activity in vitro and in vivo on phytopathogenic fungi, structure–activity relationship (SAR) and action mechanism. The results showed that most of the compounds had potent and broad-spectrum antifungal activity in vitro at 50 μg/mL. Among the compounds, 2-bromobenzyl propiolate (3h) displayed the highest comprehensive activity with total activity index (TAI) of 4.57 against all the eight test fungi followed by 3-fluorobenzyl propiolate (3c) (TAI = 4.53), superior to positive fungicides thiabendazole (TAI < 4.12) and/or azoxystrobin (TAI < 2.90). Relative to the other fungi, Fusarium solani and Fusarium graminearum revealed higher total susceptibility indexes (TSI) of 11.1 and 8.98, respectively, for all compounds. 3h and 3g (4-chlorobenzyl propiolate) gave the smallest EC50 values of 0.86 and 0.67 μg/mL against F. solani and F. graminearum, respectively, superior or comparable with thiabendazole and azoxystrobin. As a representative, 3h at 200 μg/mL displayed 100% protection on F. solani infections on potatoes over 7 days and high safety for plant growth. In antifungal mechanism, 3h was able to change mycelial morphology, destroy the structures of both hypha and cell membrane, increase the intracellular ROS level, decrease the intracellular mitochondrial membrane potential level, and change the permeability of the cell membrane. The SAR showed that ethynyl is a key group for the activity, and the presence of halogen atoms at the 2-site of the benzene ring can significantly improve the activity in most cases. Thus, benzyl propiolate can be considered a novel antifungal lead compound, while 3h can be considered a promising fungicide candidate to develop new agricultural fungicides.
研究领域:
农业化学
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植物病理学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 25
·14915-14927
·
IF 3.119
Yiqiang Yu,Kai Liu,Zhuo Wen,Weicai Liu,Lei Zhang,Jiansheng Su
Zinc-incorporated biomaterials show promoting effects on osteogenesis; however, excessive zinc ions lead to cytotoxic reactions and also have other adverse effects. Therefore, the double-edged effects of Zn2+ microenvironments on osteogenesis may become critical issues for new material development. This study systematically investigated the bidirectional influences of diverse Zn2+ microenvironments on the cell adhesion, proliferation, osteogenic differentiation and apoptosis of rBMSCs. Furthermore, the mechanisms of zinc-induced osteogenic differentiation of rBMSCs and of cell apoptosis induced by high concentration of Zn2+ were both discussed in detail. The results indicated that the Zn2+ microenvironments of 2 μg mL−1 and 5 μg mL−1 effectively improved the initial adhesion and proliferation of rBMSCs, while that of 15 μg mL−1 had exactly the opposite effect. More importantly, the suitable Zn2+ microenvironments (2 μg mL−1 and 5 μg mL−1) moderately increased the intracellular Zn2+ concentration by regulating zinc transportation, and then activated the MAPK/ERK signaling pathway to induce the osteogenic differentiation of rBMSCs. In contrast, the high Zn2+ concentration (15 μg mL−1) not only inhibited the osteogenic differentiation of rBMSCs by damaging intracellular zinc homeostasis, but also induced rBMSC apoptosis by enhancing intracellular ROS generation. The current study clarified the double-edged effects of Zn2+ microenvironments on the osteogenic properties of rBMSCs and the related mechanisms, and may provide valuable guidance for optimizing the design of zinc-doped biomaterials and zinc-based alloys.
研究领域:
生物材料
·
细胞生物学
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组织工程
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 12
·1902933
·
IF 15.84
Jiaojiao Wu,Peng Ning,Rui Gao,Qishuai Feng,Yajing Shen,Yifan Zhang,Yingze Li,Chang Xu,Yao Qin,Gustavo R. Plaza,Qianwen Bai,Xing Fan,Zhenguang Li,Yu Han,Maciej S. Lesniak,Haiming Fan,Yu Cheng
Reactive oxygen species (ROS), a group of oxygen derived radicals and derivatives, can induce cancer cell death via elevated oxidative stress. A spatiotemporal approach with safe and deep-tissue penetration capabilities to elevate the intracellular ROS level is highly desirable for precise cancer treatment. Here, a mechanical-thermal induction therapy (MTIT) strategy is developed for a programmable increase of ROS levels in cancer cells via assembly of magnetic nanocubes integrated with alternating magnetic fields. The magneto-based mechanical and thermal stimuli can disrupt the lysosomes, which sequentially induce the dysfunction of mitochondria. Importantly, intracellular ROS concentrations are responsive to the magneto-triggers and play a key role for synergistic cancer treatment. In vivo experiments reveal the effectiveness of MTIT for efficient eradication of glioma and breast cancer. By remote control of the force and heat using magnetic nanocubes, MTIT is a promising physical approach to trigger the biochemical responses for precise cancer treatment.
研究领域:
生物医学工程
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癌症研究
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纳米技术
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诊疗学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Kaiqiang Sun,Chen Yan,Xinyue Dai,Yangyang Shi,Fudong Li,Liang Chen,Jingchuan Sun,Yu Chen,Jiangang Shi
Low back pain resulting from intervertebral disc degeneration (IVDD) is a prevalent global concern; however, its underlying mechanism remains elusive. Single-cell sequencing analyses revealed the critical involvement of pyroptosis in IVDD. Considering the involvement of reactive oxygen species (ROS) as the primary instigator of pyroptosis and the lack of an efficient intervention approach, this study developed carbonized Mn-containing nanodots (MCDs) as ROS-scavenging catalytic biomaterials to suppress pyroptosis of nucleus pulposus (NP) cells to efficiently alleviate IVDD. Catalytic MCDs have superior efficacy in scavenging intracellular ROS and rescuing homeostasis in the NP microenvironment compared with N-acetylcysteine, a classical antioxidant. The data validates that pyroptosis plays a vital role in mediating the protective effects of catalytic MCDs against oxidative stress. Systematic in vivo assessments substantiate the effectiveness of MCDs in rescuing a puncture-induced IVDD rat model, further demonstrating their ability to suppress pyroptosis. This study highlights the potential of antioxidant catalytic nanomedicine as a pyroptosis inhibitor and mechanistically unveils an efficient strategy for the treatment of IVDD.
研究领域:
生物医学工程
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纳米技术
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骨科
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细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 11
·9350
·
IF 5.6
Yuhong Chen,Ying Gao,Mingan Yuan,Zhaisheng Zheng,Junfeng Yin
Candida albicansis an opportunistic human fungal pathogen, and its drug resistance is becoming a serious problem.Camellia sinensisseed saponins showed inhibitory effects on resistantCandida albicansstrains, but the active components and mechanisms are unclear. In this study, the effects and mechanisms of twoCamellia sinensisseed saponin monomers, theasaponin E1 (TE1) and assamsaponin A (ASA), on a resistantCandida albicansstrain (ATCC 10231) were explored. The minimum inhibitory concentration and minimum fungicidal concentration of TE1 and ASA were equivalent. The time–kill curves showed that the fungicidal efficiency of ASA was higher than that of TE1. TE1 and ASA significantly increased the cell membrane permeability and disrupted the cell membrane integrity ofC. albicanscells, probably by interacting with membrane-bound sterols. Moreover, TE1 and ASA induced the accumulation of intracellular ROS and decreased the mitochondrial membrane potential. Transcriptome and qRT-PCR analyses revealed that the differentially expressed genes were concentrated in the cell wall, plasma membrane, glycolysis, and ergosterol synthesis pathways. In conclusion, the antifungal mechanisms of TE1 and ASA included the interference with the biosynthesis of ergosterol in fungal cell membranes, damage to the mitochondria, and the regulation of energy metabolism and lipid metabolism. Tea seed saponins have the potential to be novel anti-Candida albicansagents.Keywords:Camellia sinensisseeds;theasaponin E1;assamsaponin A;antifungal activity;transcriptome
研究领域:
药理学
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微生物学
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分子生物学
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植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Qiqi Zhang,Xuan Wang,Yuanyuan Zhao,Zhuo Cheng,De Fang,Yingqi Liu,Gan Tian,Menghuan Li,Zhong Luo
Low-dose radiotherapy (LDR) has shown significant implications for inflaming the immunosuppressive tumor microenvironment (TME). Surprisingly, we identify that FABP-dependent lipid droplet biogenesis in tumor cells is a key determinant of LDR-evoked cytotoxic and immunostimulatory effects and developed a nanointegrated strategy to promote the antitumor efficacy of LDR through cooperative ferroptosis immunotherapy. Specifically, TCPP-TK-PEG-PAMAM-FA, a nanoscale multicomponent functional polymer with self-assembly capability, was synthesized for cooperatively entrapping hafnium ions (Hf4+) and HIF-1α-inhibiting siRNAs (siHIF-1α). The TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α nanoassemblies are specifically taken in by folate receptor-overexpressing tumor cells and activated by the elevated cellular ROS stress. siHIF-1α could readily inhibit the FABP3/7 expression in tumor cells via HIF-1α-FABP3/7 signaling and abolish lipid droplet biogenesis for enhancing the peroxidation susceptibility of membrane lipids, which synergizes with the elevated ROS stress in the context of Hf4+-enhanced radiation exposure and evokes pronounced ferroptotic damage in vital membrane structures. Interestingly, TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α-enhanced ferroptotic biomembrane damage also facilitates the exposure of tumor-associated antigens (TAAs) to promote post-LDR immunotherapeutic effects, leading to robust tumor regression in vivo. This study offers a nanointegrative approach to boost the antitumor effects of LDR through the utilization of tumor-intrinsic lipid metabolism.
研究领域:
肿瘤学
·
放射肿瘤学
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纳米技术
·
免疫疗法
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2019
·
IF 5.667
Yixian Zhang,Haolan Zhang,Zhengwei Mao,Changyou Gao
Although the negative impacts of particulate matter (PM2.5) on human health have been well recognized, very few efforts have been paid to find new strategies to suppress the toxicity of PM2.5 both in vitro and in vivo. In this study, reactive oxygen species (ROS)-responsive nanoparticles made of poly(1,4-phenleneacetonedimethylene thioketal) (PPADT) were used to load immunosuppressant drug tacrolimus (FK506) with a drug loading efficiency of around 44%. The PPADT particles showed very good ROS-responsiveness and were degraded in an oxidation environment. By exhausting intracellular ROS, they could effectively suppress the toxicity of A549 lung epithelial cells and RAW264.7 macrophages induced by the PM2.5 particulates collected from three different regions in China. Moreover, the inflammatory response of PM2.5 could also be significantly suppressed, showing much better performance than the free FK506 drugs both in vitro and in vivo. This concept-proving research demonstrates the promising application for the ROS-sensitive drug release particles in dispelling the toxicity and suppressing the inflammation of PM2.5 pollutes, shedding a new light in the design and applications of stimuli-responsive systems in the bionanotechnology and healthcare fields.
研究领域:
纳米技术
·
生物医学工程
·
环境科学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Lei Xu,Yaling Wang,Sangyu Hu,Yuzhu Pei,Chenliang Qian,Wenjie Xue,Gao Zhang,Song Wu,Xinxin Si,Xuming Deng,Jie Xia,Jianfeng Wang
To date, the abuse of antibiotics and a gradual decline in novel antibiotic discovery enlarge the threat of drug-resistant bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA). Herein, inspired by the unique structures and antibacterial activities of 2-quinolones, a class of novel 2-quinolones with substituted pyridines was synthesized. Notably, compound 11, the derivative with a methylpyridine fragment, showed potent antibacterial and antibiofilm activities, especially for MRSA strains (MIC = 0.02–0.04 μg/mL). A mechanistic study of compound 11 revealed that the increase of intracellular ROS and acceleration of the TCA cycle, which reprogrammed the bacterial metabolism, eventually triggered membrane damage and bacterial death. Most importantly, compound 11, with antibacterial and anti-inflammatory properties, accelerated the reconstruction and healing of MRSA-infected cutaneous wounds by decreasing bacterial loads, attenuating inflammation, and promoting angiogenesis. Overall, these findings provide a novel multifunctional chemotype with broad-spectrum antibacterial activity and highlight a promising strategy for MRSA-infected wound healing.
研究领域:
药理学
·
微生物学
·
化学
·
传染病学
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Hang Jia,Xuejun Zeng,Shiqi Fan,Rui Cai,Zhouli Wang,Yahong Yuan,Tianli Yue
The severe bacterial infection and chronic wound healing caused by the abuse of antibiotics threaten the public health, which calls the need for the development of novel antibacterial agents and alternative therapeutic strategies. Herein, magnetic carboxymethyl cellulose-ε-polylysine hybrids (FCE) were synthesized via a facile one-pot coprecipitation method and further used as matrix to anchor silver nanoparticles (Ag NPs). The as-resulted Ag/FCE hybrids were employed to inactivate pathogenic bacteria and accelerate bacteria-infected wound healing with the assistance of H 2 O 2 . In vitro investigation revealed the combination of hydroxyl radical (·OH) originated from low concentration of H 2 O 2 catalyzed by Ag/FCE and the antimicrobial activity of Ag NPs endowed effective antibacterial performance to the hybrids against both Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). Investigation on antibacterial mechanism indicated antibacterial activity of the synergetic strategy was achieved by destroying bacterial cell integrity, arresting metabolic, producing intracellular ROS, and oxidizing GSH. Additionally, in vivo assay exhibited Ag/FCE possessed satisfactory biocompatibility and effectively accelerated S. aureus -infected wound healing with the presence of low concentration of H 2 O 2 . Altogether, the presented results supported the great potential application of the synergistic antibacterial strategy for the therapy of bacterial-infected wound healing.
研究领域:
材料科学
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纳米技术
·
生物医学工程
·
药学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Yanling Xiao,Yuying Yuan,Manshan Liang,Jiahao Ni,Lichao Yu,Zu-Sheng Huang,Bing Du,Yun-Yun Quan
Fluorescence imaging-guided photodynamic therapy (PDT) is considered as an ideal alternative strategy to treat tumors. However, insufficient supply of oxygen in solid tumor tissue, aggregation-caused quenching (ACQ) of photosensitizers (PSs), poor targeting-specificity of cancer cells and short wavelengths of emission are representative obstacles for effective PDT. In this paper, three D-π-A structured PSs TSB-OH , TSBPy-OH , TSBPy-DNT with aggregation induced emission (AIE) properties and integrated type I and type II ROS generation were synthesized by modulating distinct acceptor units. Among them, TSBPy-OH is optimal with multiple advantages including near-infrared emission, good biocompatibility , remarkably intracellular ROS production ability, mitochondria targeting capability inducing cell apoptosis and enhancing PDT, and long-term tumor retention ability for imaging-guided photodynamic therapy. More importantly, efficient in vitro cancer cells damage, in vivo tumor ablation and ignorable damage in major organs during PDT are demonstrated, suggesting potential capability of TSBPy-OH in safe and effective fluorescence imaging-guided PDT. This successful example of AIE theranostics design would provide a reference for the modification of D-π-A structure organic AIEgens.
研究领域:
癌症治疗
·
光动力疗法
·
材料科学
·
生物医学工程
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）