CHEMISTRY OF MATERIALS
·
2018
·
IF 9.89
Ziyang Cao,Yinchu Ma,Chunyang Sun,Zidong Lu,Zeyu Yao,Junxia Wang,Dongdong Li,Youyong Yuan,Xianzhu Yang
Drug delivery systems with remotely controlled drug release capability are rather attractive options for cancer therapy. Herein, a reactive oxygen species (ROS)-sensitive polymeric nanocarrier TK-PPE@NPCe6/DOX was explored to realize remotely controlled drug release by light-activated size shrinkage. The TK-PPE@NPCe6/DOX encapsulating chlorin e6 (Ce6) and doxorubicin (DOX) was self-assembled from an innovative ROS-sensitive polymer TK-PPE with the assistance of an amphiphilic copolymer poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL). Under the 660 nm red light irradiation, ROS generated by the encapsulated Ce6 were capable of cleaving the TK linker in situ, which resulted in the rapid degradation of the TK-PPE@NPCe6/DOX core. Consequently, the size of TK-PPE@NPCe6/DOX shrank from 154 ± 4 nm to 72 ± 3 nm, and such size shrinkage affected further triggered rapid DOX release. As evidenced by both in vitro and in vivo experiments, such ROS-sensitive polymeric nanocarriers with light-induced size shrinkage capability offer remarkable therapeutic effects in cancer treatment. This concept provides new avenues for the development of light-activated drug delivery systems for remotely controlled drug release in vivo.
研究领域:
生物材料学
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肿瘤学
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药剂学
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Han Sun,Juan Xu,Yangyufan Wang,Siyu Shen,Xingquan Xu,Lei Zhang,Qing Jiang
Large bone defects resulting from fractures and disease are a major clinical challenge, being often unable to heal spontaneously by the body's repair mechanisms. Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration. However, replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells. Therefore, reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair. Herein, we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels (CPP-L/GelMA) as a “bone microenvironment regulative hydrogel” to reverse the hypoxic microenvironment in bone defects region. CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase (CAT) and ROS-responsive oxygen-releasing nanoparticles ( [email protected] /PPS) co-loaded liposome (CCP-L) and GelMA hydrogels. Under hypoxic condition, CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks. The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis. Finally, CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway. Hence, CPP-L/GelMA, as a bone microenvironment regulative hydrogel for bone tissue respiration, can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region, possessing of great clinical therapeutic potential.
研究领域:
组织工程
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生物材料
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再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2025
·
IF 4.6
Ziyan Liu,Jingyu Wang,Wei Zhang,Huiwen Kang,Danyang Huang,Ziyan Wang,Guangyu Jiang,Ai Gao
The continuous accumulation of senescent hematopoietic stem progenitors (HSPCs) contributes to hematopoietic damage. Benzene is a confirmed human carcinogen, and its damage to HSPCs is a key event in benzene poisoning. However, whether the environmental dose of benzene is involved in HSPC damage by inducing cellular senescence has not been reported. Here, male C57BL/6 J mice were exposed to benzene vapour for 12 weeks (0, 10, 50 ppm), and mouse hematopoietic progenitor cell line FDC-P1 was exposed to benzene metabolite 1,4-BQ for 24 h (0, 5, 10 μM). In vivo and in vitro models combined with single-cell RNA sequencing have shown that benzene and its metabolites caused senescence in whole bone marrow and hematopoietic progenitor cells. Proteomics showed that benzene exposure significantly up-regulated interferon regulatory factor 4 (Irf4) in the bone marrow. Irf4 inhibition alleviated cellular senescence and hematopoietic damage, suggesting that Irf4 is a key molecule in benzene-induced hematopoietic cell senescence. Mechanistically, benzene caused a decrease in branched-chain amino acids (BCAAs) in whole bone marrow, hematopoietic progenitor cells, and plasma, and an increase in the BCAA catabolic enzyme Bcat1, mitochondrial ROS, and Bckdh activity. Irf4 inhibition down-regulated Bcat1, alleviated mitochondrial oxidative stress-dependent Bckdh abnormality, and up-regulated BCAAs. BCAA supplementation effectively alleviated benzene-induced cellular senescence and hematopoietic damage. In conclusion, the study identified that Irf4 triggered benzene-induced hematopoietic progenitor cell senescence and hematopoietic damage by mitochondrial injury-induced excessive BCAA catabolism. This study provides new ideas on the molecular mechanism of benzene-induced hematopoietic damage from the perspective of metabolism and senescence.
研究领域:
毒理学
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血液学
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分子生物学
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环境卫生
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代谢
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Qiao Luo,Nianlan Cheng,Yongqing Yang,Ni Shao,Tianqi Nie,Jifeng Chen,Cuiqing Huang,Siqi Zhang,Yanyu Huang,Chon Man Ieong,Xiaokai Zhang,Kuan Hu,Zeyu Xiao,Liangping Luo
Myocardial ischemia-reperfusion (I/R) injury is characterized by oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis, ultimately leading to chronic cardiac dysfunction and heart failure. Current therapeutic strategies that predominantly target single biological pathways exhibit limited long-term efficacy, underscoring the necessity for multi-targeted approaches. In this study, we developed a ROS-responsive hydrogel system, S1&FT/Lipo-QCFT, tailored to deliver drugs for treating various stages of myocardial I/R injury. This system timing of drug release to achieve rapid deployment at early intervention stages and maintain sustained release thereafter. Initially, the hydrogel platform quickly releases the molecular forms of the superoxide inhibitor S1QEL1.1 and tannic acid, specifically targeting the elevated ROS levels at the I/R site to alleviate early oxidative damage and encourage macrophage polarization toward the M2 phenotype. Subsequently, the system gradually releases anti-fibrotic agent FT011, encapsulated in lipid nanocarriers, which actively counters TGF-β1-induced fibrosis and forestalls adverse ventricular remodeling, thereby enhancing long-term cardiac repair. In vivo studies demonstrated that the S1&FT/Lipo-QCFT hydrogel significantly improved cardiac function and reduced adverse ventricular remodeling. This hydrogel system provides a promising multi-targeted therapeutic strategy for comprehensive myocardial I/R injury treatment with strong potential for clinical translation.
研究领域:
药理学
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心血管医学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 4.3
Ziming Liu,Sihui Li,Pengfei Xu,Huiqin Gan,Pengfei Yue,Shuying Xie,Zixia Zhang,Weifeng Zhu,Zhiyu Guan
Objective To prepare chitosan-loaded nanoparticles (NPs) that enhance the oral bioavailability of puerarin (Pur) and render it responsive to reactive oxygen species (ROS). Significance This research makes substantial progress towards the theory of intelligent drug delivery, offering a new reference for combining Pur with other natural medicinal active ingredients. Methods The acylation reaction between chitosan and ROS-sensitive 3-carboxyphenylboronic acid (PBA) was used to synthesise ROS-sensitive phenylboronylated chitosan (PBACS). Subsequently, PBACS-PBA-Pur-NPs and PBACS-TPP-Pur-NPs were prepared via ion gelation after the addition of PBA and sodium tripolyphosphate(TPP), respectively. The physicochemical and functional properties of both NPs were compared, and their differences were preliminarily studied through molecular docking. Results Reactive oxygen species-sensitive PBACS was successfully synthesised. Of the two NPs prepared, PBACS-TPP-Pur-NPs had a size of 127.2 ± 0.80 nm, polydispersity index (PDI) of 0.129 ± 0.0008, and an encapsulation rate of 95.75 ± 0.387%, whereas PBACS-PBA-Pur-NPs had a size of 149.8 ± 0.1414 nm, PDI of 0.389 ± 0.0012, and an encapsulation rate of 91.77 ± 0.279%. The micromorphology of the PBACS-TPP-Pur-NPs exhibited better physical properties. However, PBACS-PBA-Pur-NPs demonstrated a faster in vitro release and more significant in vitro anti-inflammatory effects. Pharmacokinetically, the AUC 0-24 , T max , and C max of PBACS-PBA-Pur-NPs were 3.485, 2.117, and 3.339 times higher, respectively, than those of Pur. The AUC 0-24 , T max , and C max of PBACS-TPP-Pur-NPs were 2.41, 1.33, and 2.03 times higher, respectively, than those of Pur. Molecular simulation revealed that the binding energy of PBACS-PBA-Pur -NPs was approximately -4.34 kcal/mol and that of PBACS-TPP-Pur-NPs was even lower, approximately -5.93 kcal/mol, suggesting that the NPs prepared with TPP are more densely packed than those designed with PBA, resulting in slower and reduced drug release. Conclusion The NPs constructed in this study effectively reduced inflammatory factors at the disease site, providing a theoretical and experimental basis for the application of nano drugs in inflammatory disease models. In addition, the molecular docking study of the two NPs offered insights into the relationship between the release and structure of subsequent nano drugs.
研究领域:
药学
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纳米技术
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药物递送系统
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药代动力学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-15
·
IF 3.8
Wang Yan,Wang Shasha,Ma Chenchen,Qi Weiwei,Lv Jing,Zhang Mengqi,Wang Shibo,Wang Rui,Lu Yangyang,Qiu Wensheng
Gastric cancer (GC) is the most common malignant tumor of the gastrointestinal tract and currently has a poor clinical outcome. Turmeric’s rhizome contains a polyphenolic component called curcumin (Cur), which has been demonstrated to inhibit a variety of tumor cells, such as pancreatic, colon, lung and gastric cancers. However, it remains to be elucidated how Cur functions in GC and what molecular processes underlie it. Here, Cur showed a stronger inhibitory effect on GC cells AGS and HGC27. In addition, Cur’s inhibition of GC cells growth was accompanied by increased ROS production, triggering of the Keap1-Nrf2 signaling pathway, and increased transcription of its downstream antioxidant genes HO-1, GCLM, and NQO1. However, when a ROS scavenger NAC was used, the inhibitory effect of Cur on GC cells was reversed. Nuclear factor erythroid 2-related factor 2 (Nrf2) is overexpressed or activated in cancers to shield cancer cells from oxidative damage by responding to oxidative stress (OS). Cur has been found to act as an activator of Nrf2. Notably, compared with Nrf2 knockdown and Cur alone, the combination of the two dramatically increased Cur-induced ROS overaccumulation and inhibition of GC cells proliferation, migration, and invasive abilities. Consistent with in vitro experiments, Cur combined with Nrf2 knockdown significantly inhibited tumor growth in nude mice transplanted with AGS cells. Therefore, we concluded that Nrf2 depletion enhanced Cur therapy effect in GC by inducing the excessive accumulation of ROS, indicating that this is a promising treatment strategy.
研究领域:
肿瘤学
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药理学
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分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Lianghua Jiang,Xufeng Yang,Yijian Zhang,Dawei He,Yijun Gao,Ke Lu,Yanming Hao,Yan Gao,Daming Lu,Xiangyun Jin,Chong Li
Accelerating angiogenesis of diabetic wounds is crucial to promoting wound healing. Currently, vascular endothelial growth factor (VEGF), an angiogenesis-related bioactive molecule, is widely used in clinic to enhance wound angiogenesis, but it faces problems of inactivation and low utilization due to harsh microenvironment. Here, we developed a novel reactive oxygen species (ROS)-scavenging hydrogel aimed to polarize macrophages toward an anti-inflammatory phenotype, inducing efficient angiogenesis in diabetic wounds. This composite hydrogel with good biosafety and mechanical properties showed sustainable release of bioactive VEGF. Importantly, it could significantly reduce ROS level and rapidly improve wound microenvironment, which ensured the activity of VEGF in vitro and in vivo and successful healing eventually. At the same time, the composite hydrogel exhibited excellent antibacterial properties. In vivo results confirmed good anti-inflammatory, stimulated vascularization and accelerated wound healing attributed to the novel ROS-scavenging hydrogel, which might serve as a promising wound dressing in diabetic wound healing.
研究领域:
生物医学工程
·
伤口愈合
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材料科学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Yu-Xi Feng,Peng Tian,Yu-Juan Lin,Dan-Yang Cao,Cheng-Zhi Li,Abid Ullah
The induction of disruption in the electronic transport chain by thiocyanate (SCN − ) leads to an excessive generation of reactive oxygen species (ROS) within rice ( Oryza sativa ). Hydrogen sulfide (H 2 S) assumes a crucial role as a gaseous signaling molecule, holding significant potential in alleviating SCN − -related stress. Nevertheless, there remains a dearth of understanding regarding the intricate interplay between H 2 S and ROS in Oryza sativa amidst SCN − pollution. In this investigation, a hydroponics-based experiment was meticulously devised to explore how H 2 S-mediated modifications influence the genetic feedback network governing ROS metabolism within the subcellular organelles of Oryza sativa when exposed to varying effective concentrations (EC 20 : 24 mg SCN/L; EC 50 : 96 mg SCN/L; EC 75 : 300 mg SCN/L) of SCN − . The findings unveiled the enhanced capacity of Oryza sativa to uptake SCN − under H 2 S + SCN − treatments in comparison to SCN − treatments alone. Notably, the relative growth rate (RGR) of seedlings subjected to H 2 S + SCN − exhibited a superior performance when contrasted with seedlings exposed solely to SCN − . Furthermore, the application of exogenous H 2 S yielded a significant reduction in ROS levels within Oryza sativa tissues during SCN − exposure. To elucidate the intricacies of gene regulation governing ROS metabolism at the mRNA level, the 52 targeted genes were categorized into four distinct types, namely: initial regulatory ROS generation genes (ROS-I), direct ROS scavenging genes (ROS-II), indirect ROS scavenging genes (ROS-III), and lipid oxidation genes (ROS-IV). On the whole, exogenous H 2 S exhibited the capacity to activate the majority of ROS-I ∼ ROS-IV genes within both Oryza sativa tissues at the EC 20 concentration of SCN − . However, genetic positive/negative feedback networks emphasized the pivotal role of ROS-II genes in governing ROS metabolism within Oryza sativa . Notably, these genes were predominantly activated within the cytoplasm, chloroplasts, mitochondria, peroxisomes, and the cell wall.
研究领域:
植物生理学
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分子生物学
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环境科学
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农学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CYTOTECHNOLOGY
·
2025
·Vol. 77
·期 2
·1-18
·
IF 1.7
Zhou Yi,Luan Fengwu,Feng Xiaonan,Yu Min,Li Lu,Guo Xiaoyan,Yin Xiaolong
Chronic kidney disease (CKD) often progresses to renal fibrosis, which is characterized by excessive extracellular matrix deposition and is also linked to ferroptosis. The present study investigated how TGF-β1 induces ferroptosis and thereby contributes to renal tubular epithelial cell fibrosis. Bioinformatics was employed to identify the differentially expressed genes relevant to renal fibrosis. An in vitro TGF-β1-induced fibrosis model of HK-2 cells was established, and the cell shape index was calculated. Fer-1, NAC, and PD98059 were utilized for targeted intervention, and their mechanisms were verified by transducing cells with WISP1-targeting shRNA lentivirus. Cell morphology was examined under a microscope, and cells were collected to determine the levels of ferroptosis-related factors (Fe 2+ , MDA, GSH, and LPO). Western blotting was performed to measure the levels of ERK1/2, WISP1, and ferroptosis indicators (GPX4 and hyperoxidized PRDX4). Flow cytometry was performed to determine the ROS levels and the rate of cell ferroptosis. TGF-β1 induced the transformation of HK-2 cells into fibroblast-like cells, leading to increased ROS levels, activation of the ERK1/2-WISP1 signaling pathway, and upregulation of ferroptosis and fibrosis-related factors. However, these effects could be effectively inhibited through pretreatment with Fer-1, NAC, and PD98059 individually, which further validated the involvement of the ERK1/2-WISP1 signaling pathway. In addition, WISP1 knockdown suppressed the cell transformation into fibroblast-like cells as well as the ferroptosis process, thereby reducing the expression levels of ferroptosis and fibrosis-related factors. The present study substantiated the process through which TGF-β1 elicits the production of ROS and triggers ferroptosis via the ERK1/2-WISP1 signaling pathway to facilitate the development of renal tubular epithelial cell fibrosis.
研究领域:
细胞生物学
·
分子生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Chang Liu,Rui Zhou,Baiqiao Chen,Xinran Yan,Lei Guo,Yixin Tang,Xu Zuo,Xiaoping Guo,Haiyang Yu,Jie Chen,Zhaopei Guo,Fang Wang,Caina Xu
The pathogenesis of acute lung injury (ALI) is characterized by an uncontrolled inflammatory response, marked by excessive production of reactive oxygen species (ROS) and the infiltration of inflammatory cells, particularly macrophages, which play a pivotal role in disease progression. The synergistic effect of ROS scavenging and macrophage repolarization provides a promising strategy for effective ALI treatment. Herein, we developed a novel type of self-assembling nanomicelles, which were composed of poly-L-glutamic acid (PLG) and 4-Hydroxymethyl phenylboronic acid (PBA). The nanomicelles (PPDex micelles) had a high drug-loading capacity for dexamethasone (Dex) based on boronic ester bonds, which exhibited reversible cleavage under inflammatory conditions characterized by elevated levels of ROS or decreased pH values. These PPDex micelles revealed rapid drug-responsive release behavior in the inflammatory environment, and in vivo studies demonstrated their efficacy in modulating cytokines, inhibiting oxidative stress, and promoting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, which ultimately suppressed the progression of ALI. Moreover, the PPDex micelles had the effective ability to effectively suppress the NF-кB and ROS/NLRP3 inflammatory pathways. Therefore, this study presented a novel and potent therapeutic strategy for ALI treatment, which could promote the clinical application of polymer nanomicelles in the treatment of ALI.
研究领域:
药理学
·
纳米医学
·
呼吸病学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Xitong Ren,Haochen Yao,Jiali Sun,Fuxin Xue,Linjie Cui,Yajun Xu,Kazuo Sakurai,Na Shen,Zhaohui Tang
Immune checkpoint blockade (ICB) therapy represents a promising approach widely embraced for its sustained efficacy upon activation of the body’s immune responses. Nonetheless, its effectiveness exhibits significant variability among patients, with a response rate below 30 %. A key limitation is the insufficient tumor infiltration and specific priming of CD8 + T cells. To address this, we develop ROS-responsive TLR7/8 nanoagonists {methoxy poly(ethylene glycol)- b -poly-[(N-2-hydroxyethyl)-aspartamide]- g -thioketal-R848}, designated as R848 NPs, wherein the C-4 amino of R848 is chemically blocked to enable selective release under endogenous tumor ROS conditions, thereby mitigating the severe systemic cytokine storms associated with R848. Additionally, ultrasound (US) is employed to induce immune cell death and facilitate intratumoral enrichment of R848 NPs. The proposed combination treatment, R848 NPs+US, effectively enhances antigen presentation by dendritic cells (DCs), facilitates intratumoral distribution of active R848, mitigates systemic inflammatory responses, promotes the release of damage-associated molecular patterns, and upregulates the expression of costimulatory molecules on DCs. Ultimately, R848 NPs+US plays a crucial role in bolstering CD8 + T cells immunity, synergizing with αPDL1 for CT26 tumor suppression (rate: 99.0 %, Q value: 1.68), eliciting memory immunity, and preventing tumor rechallenge. This work provides a novel strategy to potentiate the cancer immunity and a guidance for ICB therapy.
研究领域:
癌症免疫疗法
·
纳米技术
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Wen Zhou,Yuwan Chen,Wenxin Fu,Xinwei Li,Yufei Xia,Qun Zhao,Baofeng Zhao,Yukui Zhang,Kaiguang Yang,Lihua Zhang
The study of in situ conformations and interactions of mitochondrial proteins plays a crucial role in understanding their biological functions. Current chemical cross-linking mass spectrometry (CX-MS) has difficulty in achieving in-depth analysis of mitochondrial proteins for cells without genetic modification. Herein, this work develops the reactive oxygen species (ROS)-responsive cross-linker delivery nanoparticles (R-CDNP) targeting mitochondria. R-CDNP contains mitochondria-targeting module triphenylphosphine, ROS-responsive module thioketal, loading module poly(lactic-co-glycolic acid) (PLGA), and polyethylene glycol (PEG), and cross-linker module disuccinimidyl suberate (DSS). After targeting mitochondria, ROS-triggered cross-linker release improves the cross-linking coverage of mitochondria in situ. In total, this work identifies 2103 cross-linked sites of 572 mitochondrial proteins in HepG2 cells. 1718 intra-links reveal dynamic conformations involving chaperones with ATP-dependent conformation cycles, and 385 inter-links reveal dynamic interactions involving OXPHOS complexes and 27 pairs of possible potential interactions. These results signify that R-CDNP can achieve dynamic conformation and interaction analysis of mitochondrial proteins in living cells, thereby contributing to a better understanding of their biological functions.
研究领域:
生物化学
·
细胞生物学
·
分子生物学
·
纳米技术
✓ 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）