Diabetes & Vascular Disease Research
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2024
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IF 2.8
Yuxin Hu,Zhen Li,Hongxue Li,Qian Xu,Chengye Xu,Wenjian Lin,Xuefei Ma,Ming Hao,Hongyu Kuang
Human microglia (HMC) are stress-induced inflammatory cells of the retina. It is unknown whether severe hypoglycaemia causes inflammation in microglia, affects the permeability of human retinal microvascular endothelial cells (HRMECs), and causes retinal damage. This study aimed to explore the effects of severe hypoglycaemia on retinal microglial inflammation and endothelial cell permeability and evaluate the damage caused by hypoglycaemia to the retina. The CCK-8 assay was used to measure cell viability. Western blotting was used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. ELISA was used to detect IL-1β, IL-6, and TNF- α. Transmission electron microscopy (TEM) and haematoxylin and eosin staining were used to observe the retinal structure. Immunohistochemistry and immunofluorescence staining assays were also used to detect IL-1β, IL-6, TNF- α, claudin-1, and occludin expression. Severe hypoglycaemia promoted inflammation in HMC3 cells. Inflammation caused by hypoglycaemia leads to the decreased expression of tight junction proteins. In vivo, severe hypoglycaemia induced structural damage to the retina, increased the expression of inflammatory factors, and decreased the expression of tight junction proteins. Our results suggest that severe hypoglycaemia leads to acute retinal inflammation, affecting the permeability of HRMECs and causing retinal damage.
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International Journal of Extreme Manufacturing
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2025
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IF 21.3
Wenxin Xu,Hao Tian,Yanzhen Song,Hanfeng Qin,Junbin Gao,Yichi Chen,Weichang Huang,Lin Lin,Haixin Tan,Yicheng Ye,Xiaoting Zhang,Daniela A Wilson,Guang Yang,Fei Peng,Yingfeng Tu
Ferroptosis is a recently proposed type of programmed cell death, associated with a variety of diseases including tumors. Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-cancer therapy. However, the development of ferroptosis-based nanotherapeutics was hindered by the limited penetration depth in tumors, poor active pharmaceutical ingredient loading content (API) and the systemic toxicity. Herein, self-propelled ferroptosis nanoinducers composed of two endogenous proteins, glucose oxidase and ferritin, are presented to show enhanced tumor inhibition via ferroptosis while remaining high API and biocompatibility. The accumulation of our proteomotors at tumor regions is facilitated by the active tumor-targeting effect of ferritin. The enhanced diffusion of proteomotors is then actuated by efficiently decomposing glucose into gluconic acid and H2O2, leading to deeper penetration and enhanced uptake into tumors. Under the synergistic effect of glucose oxidase and ferritin, the equilibrium between ROS and GSH was damaged, leading to lipid peroxidation. As a result, by inducing ferroptosis, our self-propelled ferroptosis nanoinducers exhibit enhanced tumor inhibition with negligible systemic toxicity. This work paves a way for constructing a biocompatible cancer treatment paradigm with enhanced diffusion utilizing only two endogenous proteins, centered around the concept of ferroptosis.
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Nanoscale
·
2024
·Vol. 16
·期 8
·4095-4104
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IF 5.8
Xinyi Cai,Tiantian Xu,Rui Ding,Dou Zhang,Guiquan Chen,Wenchang Zhao,Jiajie Hou,Hong Pan,Qian Zhang,Ting Yin
In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic–photodynamic combination therapy.
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Journal of Materials Chemistry B
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2024
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IF 6.1
Nianlu Li,Gaorui Zhang,Jinhua Zhan,Dexin Yu
Fenton reaction–based chemodynamic therapy is a form of cancer therapy and its efficacy can be significantly improved by facilitating the iron ions involved catalytic reaction. In this work, iron-loaded carbonaceous nanoparticles (CNPs@Fe) with Fenton catalytic activity were fabricated and applied for chemodynamic therapy of cancer. The carbonaceous nanoparticles derived from glucose by a caramelization reaction demonstrated high biocompatibility. Besides, aromatic structures in the carbonaceous nanoparticles prefer accelerating electron transfer to enhance the catalytic decomposition of H2O2, resulting in the formation of highly reactive hydroxyl radicals (•OH). At pH 6.0 (representing the weak acidity in tumor microenvironment), the Fenton catalytic activity of CNPs@Fe for decomposition of H2O2 were 15.3 times higher than that of Fe2+ and 28.3 times higher than that of Fe3O4 by chromogenic reaction. The reasons for the enhancement were explained by analyzing the chemical composition of carbonaceous using high-resolution mass spectra. The developed Fenton agent also demonstrates a significant therapeutic effectiveness and little side effects by in vitro and in vivo anticancer studies. This work has put forward a novel approach to promote generation of reactive oxygen species (ROS) for chemodynamic therapy of cancer.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Xuan He,Dan Liang,Jun Zhou,Kangjing Li,Beibei Xie,Chunyun Liang,Cong Liu,Zhiyong Chen,Xinxin Chen,Ao Long,Shufang Zhuo,Xiaoping Su,Ying Luo,Wenxia Chen,Fengfeng Zhao,Xinglu Jiang
The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
·
IF 9.4
Tianyou Wang,Tao Liu,Zekai Li,Di Wu,Xiaolong Zhao,Leyong Zeng
Mesoporous platinum (mPt) nanozyme possessed enzyme-like property of catalase (CAT) and peroxidase (POD), but the insufficient hydrogen peroxide (H 2 O 2 ) concentration severely restricted its application in photodynamic therapy (PDT) and catalytic therapy. Herein, by depositing ultrasmall gold nanoparticles (AuNPs) and modifying photosensitizer IR808, a multifunctional nanozyme (mPt@Au-IR808) was designed to promote PDT/catalytic therapy through cascade enzyme-like reactions of glucose oxidase (GOx) and CAT/POD. In tumor microenvironment, the CAT-like oxygen (O 2 ) generation improved the PDT efficacy, and the POD-like hydroxyl radical (·OH) generation achieved endogenous catalytic therapy. Using the GOx/CAT-like activities and endogenous H 2 O 2 , the yields of singlet oxygen and ·OH were significantly promoted. Furthermore, mPt@Au-IR808 showed higher photothermal conversion efficiency (41.2%) than mPt (36.1%). By combining the photothermal therapy and enhanced PDT/catalytic therapy, the developed mPt@Au-IR808 nanozyme showed excellent anti-tumor efficacy, which will be promising as cascade nanozyme to promote photo/catalytic therapy.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Gangwan Zhang,Linna Chang,Xingguo Xu,Longyue He,Di Wu,Haiying Wei,Leyong Zeng
Transition metal-coordinated porphyrin metal-organic frameworks (MOFs) were perspective in photodynamic therapy (PDT) and catalytic therapy. However, the tumor hypoxia and the insufficient endogenous hydrogen peroxide (H 2 O 2 ) seriously limited their efficacies. Herein, by encapsulating ultrasmall iridium (Ir) and modifying glucose oxidase (GOx), an iron-coordinated porphyrin MOF (Fe-MOF) nanoplatform (Fe-MOF@Ir/GOx) was designed to strengthen PDT/catalytic therapy by producing reactive oxygen species (ROS) storm. In this nanoplatform, Fe-MOF showed glutathione (GSH)-responsive degradation, by which porphyrin, GOx and ultrasmall Ir were released. Moreover, ultrasmall Ir possessed dual-activities of catalase (CAT)-like and peroxidase (POD)-like, which provided sufficient oxygen (O 2 ) to enhance PDT efficacy, and hydroxyl radical (·OH) production was also improved by combining Fenton reaction of Fe 2+ . Further, GOx catalyzed endogenous glucose produced H 2 O 2 , also reduced pH value, which accelerated Fenton reaction and resulted in generation of ROS storm. Therefore, the developed Fe-MOF@Ir/GOx nanoplatform demonstrated enhanced PDT/catalytic therapy by producing ROS storm, and also provided a promising strategy to promote degradation/metabolism of inorganic nanoplatforms.
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International Journal of Pharmaceutics-X
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2024
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IF 5.2
Dan Yang,Min Zhao,Yihe Huang,Liwen Chen,Jiqin Fang,Jiaonan Liu,Miao Wang,Chunjie Zhao
The incidence of acetaminophen-induced liver injury has increased, but effective prevention methods are limited. Although luteolin has hepatoprotective activity, its low solubility and bioavailability limit its applications. Cyclodextrin metal-organic frameworks (CD-MOFs) possess 3D-network structures and large inner cavities, which make them excellent carriers of poorly soluble drugs. In this study, we used CD-MOFs as carriers to improve the dissolution of luteolin and assessed their antioxidant activity, bioavailability, and hepatoprotective effects. Luteolin was loaded into β-CD-MOF, γ-CD-MOF, β-CD, and γ-CD, and characterized by powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TGA). Our results showed that luteolin-β-CD-MOF was the most stable. The main driving forces were hydrogen bonds and van der Waals forces, as determined by molecular simulation. The loading capacity of luteolin-β-CD-MOF was 14.67 wt%. Compared to raw luteolin, luteolin-β-CD-MOF exhibited a 4.50-fold increase in dissolution and increased antioxidant activity in vitro . Luteolin-β-CD-MOF increased the bioavailability of luteolin by approximately 4.04- and 11.07-fold in healthy rats and liver injured rats induced by acetaminophen in vivo , respectively. As determined by biochemical analysis, luteolin-β-CD-MOF exhibited a better hepatoprotective effect than raw luteolin in rats with acetaminophen-induced liver injury. This study provides a new approach for preventing acetaminophen-mediated liver damage.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Subramani Kandhasamy,Baofang Wu,Jiayin Wang,Xiaojing Zhang,Gao Hongzhi,Da-Peng Yang,Yiming Zeng
Hydrogels incorporating natural biopolymer and adhesive substances have extensively been used to develop bioactive drugs and to design cells encapsulating sturdy structure for biomedical applications. However, the conjugation of the adhesive in most hydrogels is insufficient to maintain long-lasting biocompatibility inadequate to accelerate internal organ tissue repair in the essential native cellular microenvironment. The current work elaborates the synthesis of charged choline-catechol ionic liquid (BIL) adhesive and a hydrogel with an electronegative atom rich polyphenol (PU)-laden gelatinmethacryloyl (GelMA) to improve the structural bioactivities for in vivo tracheal repair by inducing swift crosslinking along with durable mechanical and tissue adhesive properties. It was observed that Bioactive BIL and PU exhibited potent antioxidant (IC 50 % of 7.91 μg/mL and 24.55 μg/mL) and antibacterial activity against E. coli , P. aeruginosa and S. aureus . The novel integration of photocurable GelMA-BIL-PU revealed outstanding mechanical strength, biodegradability and sustained drug release. The in vitro study showed exceptional cell migration and proliferation in HBECs, while in vivo investigation of the GelMA-BIL-PU hydrogel on a rat's tracheal model revealed remarkable tracheal reconstruction, concurrently reducing tissue inflammation. Furthermore, the optimized GelMA-BIL-PU injectable adhesive bioink blend demonstrated superior MSCs migration and proliferation, which could be a strong candidate for developing stem cell-rich biomaterials to address multiple organ defects.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Chuanqi Feng,Lumin Wang,Dashuai Zhang,Longlong Geng,Lianwen Zhou,Ling Wang,Guanfeng Tian,Qi Tang,Jinyan Hu,Bijiang Geng,Lang Yan
The efficacy of electron-hole separation in a single sonosensitizer and the complexities of the tumor microenvironment (TME) present significant challenges to the effectiveness of sonodynamic therapy (SDT). Designing efficient sonosensitizers to enhance electron-hole separation and alleviate TME resistance is crucial yet challenging. Herein, we introduce a novel Z-scheme heterojunctions (HJs) sonosensitizer using Fe-doped carbon dots (CDs) as auxiliary semiconductors to sensitize cubic Cu 2 O (Fe-CDs@Cu 2 O) for the first time. Fe-CDs@Cu 2 O demonstrated enhanced SDT effects due to improved electron-hole separation. Additionally, the introduction of Fe ions in CDs synergistically enhances Fenton-like reactions with Cu ions in Cu 2 O, resulting in enhanced chemodynamic therapy (CDT) effects. Moreover, Fe-CDs@Cu 2 O exhibited rapid glutathione (GSH) depletion, effectively mitigating TME resistance. With high rates of 1 O 2 and OH generated by Fe-CDs@Cu 2 O, coupled with strong GSH depletion, single drug injection and ultrasound (US) irradiation effectively eliminate tumors. This innovative heterojunction sonosensitizer offers a promising pathway for clinical anti-tumor treatment.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Qian Yu,Xian Qiu,Jing Zhong,Chao Cao,Yuechan Liao,Zhiwei Zeng,Dawei Zhang,Chunyan Yan
Acorus tatarinowii , a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF- α , IL-1 β , PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50–3 was obtained from AT50. Structural analysis indicated ATP50–3 consisted of α -L-Ara f -(1→, →2)- α -L-Ara f -(1→, →3)- α -L-Ara f -(1→, →5)- α -L-Ara f -(1→, α -D-Xyl p -(1→, →3,4)- β -D-Xyl p -(1→, →3)- α -D-Gal p -(1→, →3,6)- α -D-Gal p -(1→, →6)-4-OAc- α -D-Gal p -(1→, →3,4,6)- α -D-Gal p -(1→, →4)- α -D-Glc p -(1→, →2,3,6)- β -D-Glc p -(1→, →4,6)- α -D-Man p -(1→, →3,4)- α -L-Rha p -(1→, →4)- α -D-Gal p A-(1→, and →4)- α -D-Glc p A-(1 → residues and terminated with Xyl and Ara. Additionally, ATP50–3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50–3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.
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ACS Central Science
·
2025
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IF 10.4
Qifang Wu,Yingna Li,Yunyun Zhao,Ruifen Zhang,Jingyang Tong,Chunlei Ji,Yiming Zhao,Mingjiang Wu,Xiaosheng Jin,Dandan Wang,Haibin Tong,Liwei Sun,Fangbing Liu
Excessive fructose intake drives intestinal aging and impairs intestinal stem cell (ISC) function, yet effective therapeutic interventions remain elusive. Astragaloside IV (AS-IV), a natural saponin from Astragalus membranaceus, has been widely recognized for its antiaging, anti-inflammatory, and gut-protective properties. Here, we revealed that AS-IV alleviates fructose-induced intestinal metabolic senescence via direct inhibition of ketohexokinase (KHK), the key rate-limiting enzyme in fructose metabolism. Molecular docking and site-directed mutagenesis identified Asn261 and Ala226 as distinct binding sites for AS-IV on KHK, with Asn261 also serving as a critical catalytic residue that is essential for KHK activity. Mutation at Asn261 abolished KHK enzymatic function, reduced the accumulation of fructose-derived metabolites such as palmitic acid and ceramide, and thereby prevented fructose-induced ISC cycle arrest. AS-IV’s therapeutic efficacy was validated across Drosophila, murine intestinal organoids, and mice, where treatment consistently reversed high-fructose-induced intestinal metabolic senescence phenotypes, restored ISC proliferation, and preserved ISC homeostasis. These findings indicate that KHK is a previously unrecognized molecular target of AS-IV and reveal a conserved mechanism by which AS-IV modulates fructose metabolism to interfere with gut aging. Our results highlight its therapeutic potential in treating fructose-driven intestinal aging and associated metabolic disorders.
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