Stem Cell Research & Therapy
·
2018
·Vol. 9
·期 1
·1-11
·
IF 4.963
Li Qiang,Yin Yating,Zheng Yuqing,Chen Feifei,Jin Peisheng
Background Increased apoptosis in adipose tissue-derived stem cells (ADSCs) limits their application in treating diabetes complications. Autophagy is a molecular process that allows cells to degrade and recover damaged macromolecules, and closely interacts with apoptosis. The aim of the present study was to investigate the potential role of autophagy in ADSC apoptosis induced by high glucose.Methods Human ADSCs were cultured in normal or high-glucose medium for 6 h, 12 h, or 24 h. The effects of high glucose on ADSC autophagy, reactive oxygen species (ROS) production, and apoptosis were evaluated. The impact of autophagy on ROS production and apoptosis was explored by treatment with rapamycin or 3-methyladenine (3-MA). The c-jun kinase (JNK) signaling pathway was investigated by pharmacological disruption of SP600125.Results ADSCs subjected to high glucose stress showed an obvious induction of autophagy and apoptosis and a significant increase in intracellular ROS levels. The JNK signaling pathway was confirmed to be involved in high glucose-induced autophagy. Pre-treatment with SP600125 or N-acetylcysteine reversed the effects of high glucose on the JNK signaling pathway and autophagy-related proteins. Pretreatment of ADSCs with 3-MA under high glucose stress induced a further increase in ROS levels compared to those of high glucose-treated cells. Furthermore, ADSCs pretreated with 3-MA under high glucose stress showed a marked increase in apoptosis compared with that of the cells treated with high glucose. Conversely, pre-treatment with rapamycin inhibited the apoptosis of ADSCs.Conclusion sTaken together, our data suggest that autophagy may play a protective role in high glucose-induced apoptosis in ADSCs. ROS/JNK signaling is essential in upregulating high glucose-induced autophagy. This study provides new insights into the molecular mechanism of autophagy involved in high glucose-induced apoptosis in ADSCs.
研究领域:
细胞生物学
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分子生物学
·
糖尿病研究
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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
·
药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2025
·
IF 2.5
Kai Hu,Linlin Liang,Jian Song
Oxidative stress arises from an imbalance between excessive production of reactive oxygen species (ROS) and the body’s antioxidant defenses. In neurodegenerative diseases, this imbalance leads to ROS accumulation, causing neuronal dysfunction and cell death. Traditional drug therapies often fail to address the dynamic nature of neuroinflammation, limiting their therapeutic efficacy. To overcome this challenge, we have developed an innovative ROS-responsive injectable hydrogel. This hydrogel is designed to detect oxidative stress sensitively and release glutathione in a controlled manner, thereby modulating inflammation and restoring the damaged immune microenvironment to facilitate tissue repair. The hydrogel was synthesized by crosslinking polyvinyl alcohol (PVA) with sodium alginate modified with 3-aminophenylboronic acid (Alg-PBA). We investigated the hydrogel’s formation mechanism and analyzed how component variations affect its morphological and rheological properties. Our findings demonstrate that an optimal Alg-PBA to PVA weight ratio of 2:1 yields a hydrogel with superior mechanical strength. Glutathione (GSH) release studies confirmed the hydrogel’s pronounced ROS-responsive drug release behavior. Furthermore, biocompatibility assessments revealed that the hydrogel loaded with 100 μg/mL GSH exhibited excellent compatibility and significantly inhibited neuronal apoptosis under oxygen-glucose deprivation (OGD) conditions. This work presents a promising strategy for treating inflammation-related diseases and provides valuable insights for designing next-generation hydrogels that adapt to injury-responsive microenvironments.
研究领域:
生物材料学
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药剂学
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神经科学
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DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 8
·1845
·
IF 4.2
Sitong Lai,Bing Wang,Kunhui Sun,Fan Li,Qian Liu,Xie-An Yu,Lihe Jiang,Lisheng Wang
The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.
研究领域:
药学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Mengyao Chen,Jingxian Yang,Lulu Zhou,Xiaochun Hu,Chunhui Wang,Keke Chai,Ruihao Li,Lei Feng,Yanting Sun,Chunyan Dong,Shuo Shi
Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H2O2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe2+@UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H2O2, providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen (1O2) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1O2, resulting in the release of Fenton reagent (Fe2+) to realize CDT. Taken together, Fe2+@UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
·
IF 4.9
Ping-fu Huang,Miaomiao Ma,Hao Wu,Wen-min Niu,Lu-lu Liu,Jia-bing Tong
Purpose Rheumatoid arthritis (RA) is an autoimmune disease with systemic inflammatory. Ibuprofen (IBF) and curcumin (CUR) were the commonly therapeutic ingredients for RA treatment and the combination administration possessed the ideal efficacy, however, the low solubility and lack of targeting produced the significant obstacles for the treatment. Methods In this study, the IBF prodrug decorated with the CD44 receptors and ROS-sensitive was prepared and encapsulated with the CUR named CUR@HA-TK-IBF were designed, the characterization of CUR@HA-TK-IBF were performed in vitro and the efficacity effect were evaluated using collagen induced arthritis (CIA) model. Results The obtained product CUR@HA-TK-IBF exhibited the diameter of 137.3 ± 4.5 nm, and the morphology of the nanoparticles showed the sphericity via the TEM. In vitro release results indicated that the IBF and CUR could slowly release in the normal environment and quickly release at the H 2 O 2 environment. Furthermore, the combination of CUR and IBF could significantly decrease the expression of the proinflammatory factors and the concentration of ROS and COX-2 in vitro . The animal experiment indicated that the CUR@HA-TK-IBF could alleviate the foot tumefaction and decrease the expression of proinflammatory factors in the RA model mice. Conclusion The CUR@HA-TK-IBF developed the new approach for co-deliver the IBF and CUR, which provided a new therapeutic strategy for the treatment of RA.
研究领域:
药学
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免疫学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 7
·期 3
·460-468
·
IF 4.776
Yu Chen,Yujie Gao,Yuce Li,Ke Wang,Jintao Zhu
The combination of chemotherapy and photodynamic therapy (PDT) using polymeric nanocarriers is effective for improving therapeutic efficiency against cancer. Yet, in most reported cases, due to the lack of synergistic mechanisms, chemotherapy and PDT work independently rather than synergistically—the functions of chemotherapeutic drugs and photosensitizers in nanocarriers are independent when they are delivered to cancer cells. Here, we demonstrate the construction of reactive oxygen species (ROS)-degradable nanoparticles (NPs) based on phenylboronic pinacol ester-conjugated dextran (PPE–Dex) through a membrane-extrusion emulsification approach for the co-delivery of anticancer drug (e.g., doxorubicin, Dox) and photosensitizer (e.g., chlorin e6, Ce6). When exposed to 655 nm laser irradiation, ROS generated by encapsulated Ce6 not only induced a significant PDT effect in cancer cells, but also triggered the rapid oxidization and degradation of PPE–Dex, resulting in the quick release and enhanced intra-nuclei accumulation of Dox. In vitro cytotoxicity and combination index (CI) assay indicated that the PPE–Dex NPs offered remarkable synergistic therapeutic effects of Dox and Ce6 against cancer cells under irradiation. Furthermore, the drug release profiles can be well regulated by changing the irradiation time to satisfy different demands in various treatment programs. Our results demonstrated that such ROS-degradable polymeric NPs with light-activated disassembly capability are promising carriers for synergistic photodynamic–chemo therapy in cancer therapy.
研究领域:
癌症治疗
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纳米医学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science-Processes & Impacts
·
2023
·Vol. 25
·期 12
·1962-1973
·
IF 5.5
Jine Wang,Chen Zhang,Rui Zhao,Pei Wang,Meihua Jin,Jiujun Xu
Marine biofouling is a thorny issue that causes serious economic losses and adverse ecological impacts on marine ecosystems. Effective and promising antifouling strategies such as surface hydration, flow shear force, and lubricant injection have been developed to address this challenge. However, for the complex marine environment, they still appear inadequate. Mussels are a common fouling organism with strong surface adhesion ability. However, when hypoxia and the oxidative cross-linking reaction of 3,4-dihydroxy phenyl-L-alanine (DOPA) in the structure of adhesion proteins are disrupted, their adhesion ability will be greatly reduced. Inspired by this, we developed an effective antifouling strategy based on reactive oxygen species (ROS) scavenging using N-acetylcysteine (NAC) and evaluated its performance. As a ROS scavenger interfered with the oxidative cross-linking reaction of DOPA in an aqueous solution, the adhesion of DOPA was also affected on the surface of NAC functionalized polyvinyl chloride (PVC) (PVC-NAC). In addition, the colonization level of mussels and the adhesion rate of marine bacteria and benthic diatoms on PVC-NAC were low. The antifouling strategy proposed in this paper was eco-friendly and broad-spectrum, and may provide a new idea for solving marine biofouling and reducing the environmental and economic impacts of fouling organisms.
研究领域:
海洋生物学
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材料科学
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环境科学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2025
·
IF 6.3
Hao Deng,Xiaolu Chen,Wei Zhang,Hulin Yang,Xinyue Yang,Qiyi Zhang,Yonggang Yan
Reactive oxygen species (ROS) plays a crucial role in normal physiological activities. But hypoxia-induced oxidative stress leads to excessive accumulation of ROS in the microenvironment of bone defects, which could hinder tissue repair. Therefore, the regulation of ROS is essential for promoting bone repair. Herein, a mesoporous bioactive glass-based nanoenzyme (MBGNs@PDA@MnO 2 ) with the property to manage ROS was designed and prepared. The MBGNs@PDA@MnO 2 powders displayed excellent mineralization properties and antioxidation activity. The hydrogel with double-network structure were constructed and synthesized using oxidized chitosan (OCS) and dopamine-grafted gelatin (Gel-DA) by Schiff-base and oxidative coupling reaction, and then MBGNs@PDA@MnO 2 was incorporated into the hydrogel. Cell experiments demonstrated that the composite hydrogels could effectively reduce intracellular ROS level, and had good cytocompatibility and osteogenesis promotion capability. Hence, the composite hydrogels with ROS regulation had the potential to be a new strategy for the treatment of bone defects.
研究领域:
生物材料学
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组织工程
·
再生医学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jiayang Luo,Luyao Xu,Jing Feng,Kexin Xu,Peilin Tian,Xianyue Bai,Shihao Xu,Liewei Wen,Cuixia Lu,Jiaxing Song
Photodynamic therapy (PDT) induces apoptosis in cancer cells by generating cytotoxic reactive oxygen species (ROS); however, this effect is constrained by the intrinsic antioxidant mechanisms of the cells and the hypoxic conditions of the tumor microenvironment (TME). To overcome these limitations, a novel ferroptosis-boosted nanophotosensitizer (FCE NPs) is developed after loading alkaloid evodiamine based on an acid-responsive nanoplatform (FC NPs) composed of ferric ions and Chlorin e6 (Ce6). Upon exposure to laser irradiation, the photosensitizer Ce6 efficiently generates singlet oxygen (1O2), which depletes glutathione (GSH), thereby disrupting the redox homeostasis within tumor cells and leading to the oxidation of cellular unsaturated lipid into lipid peroxides (LPO). Additionally, the Fenton reaction between released Fe(III) ions and H2O2 in the TME produces highly cytotoxic hydroxyl radicals (•OH), a form of ROS, causing the accumulation of LPO together with 1O2 to trigger ferroptosis. Following the incorporation of evodiamine, the integrated nanoplatform FCE NPs exhibited excellent antitumor activity through high-performance ferroptosis by inhibiting a glutathione peroxidase 4 (GPX4) level. It was also observed that the key regulator of Wnt signaling pathway β-catenin was downregulated, suggesting the inhibition of FCE NPs on the Wnt signaling pathway. Therefore, this study demonstrated that the FCE NPs could lead to the explosive production of ROS and simultaneous inhibition of GPX4/GSH pathways and the Wnt signaling pathway in colorectal cancer, significantly amplifying the tumoricidal efficacy of PDT through the synergistical sensitization of ferroptosis. This approach offers a promising strategy for the clinical application of ferroptosis therapy.
研究领域:
生物学
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医学
·
肿瘤学
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生物化学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Shuying Li,Han Gao,Jielin Zhao,Guirong Wang,Guofeng Gu
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Studies have documented the antitumor activities of various polysaccharides derived from Antrodia cinnamomea (AC); however, to date, the antitumor activity of the oligosaccharide fragment related to galactomannan polysaccharide in AC remains unreported. In this study, we disclosed that the backbone tetrasaccharide derivative of AC galactomannan, designated as ACP-3, demonstrates specific binding to mannose receptors (MR) on the surface of Hep G2 cells, facilitating its cellular internalization. This interaction thereby elicited potent antiproliferative effects through dual mechanisms: ROS/JNK signaling-induced apoptosis and ROS-mediated autophagy-induced cell death. In vivo studies further validated the tumor-targeting capability of ACP-3, as monotherapy significantly suppresses the growth of H22 solid tumors. Notably, the co-administration of ACP-3 with cyclophosphamide (CTX) could synergistically enhance antitumor activity and concurrently alleviate CTX-induced adverse effects such as weight loss, hepatorenal toxicity, and immune dysfunction. These findings collectively establish ACP-3 as a promising therapeutic candidate for the treatment of HCC.
研究领域:
肿瘤学
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分子生物学
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药理学
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天然产物化学
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免疫学
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细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano-Micro Letters
·
2024
·Vol. 16
·期 1
·1-21
·
IF 31.6
Zhou Xi,Zhou Quan,He Zhaozhi,Xiao Yi,Liu Yan,Huang Zhuohang,Sun Yaoji,Wang Jiawei,Zhao Zhengdong,Liu Xiaozhou,Zhou Bin,Ren Lei,Sun Yu,Chen Zhiwei,Zhang Xingcai
The innovation of this work mainly lies in the auto-regulation of reactive oxygen species (ROS) balance effective by combination of ROS antibacterial and ROS scavenging anti-inflammatory functions with a core–shell nanoplatform (CeO 2 @ZIF-8/Au), which can not only achieve high antibacterial efficiency, but also promote wound healing, and provide a new idea for the nano-catalytic system in the field of wound healing of bacterial infection.
研究领域:
纳米技术
·
材料科学
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生物医学工程
·
伤口愈合
✓ 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）