INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhixiang Mu,Yan Yang,Guanyao Zhang,Xiaobin Yang,Qingqing Dong,Jiaying Ma,Anlin Li,Ke Li,Jiajun Hu,Xuanxin Yang,Qiuqiu Mu,Xiaojie Wang
Diabetic wound healing remains challenging due to persistent hyperglycemia-driven reactive oxygen species (ROS) accumulation and mitochondrial dysfunction. To address this, we engineered a photocurable hydrogel ( [email protected] ) composed of gelatin methacryloyl (GelMA) and bovine serum albumin methacryloyl (BSAMA) to encapsulate aucubin (Auc). Systematic evaluation of GelMA/BSAMA ratios identified the 1:1 formulation as optimal, exhibiting superior mechanical strength. The binding ability of BSAMA to Auc could realize sustained release. Furthermore, GelMA's MMP-9-responsive domains enabled accelerated Auc release in inflammatory microenvironments. The design integrates BSAMA's drug-binding capacity with GelMA's MMP-9 responsiveness to achieve spatiotemporal drug release. In vitro studies demonstrated that the hydrogel effectively scavenges ROS and restores mitochondrial membrane potential, thereby disrupting the ROS storm cycle. This antioxidative effect further suppressed the production of pro-inflammatory cytokines (IL-1β, IL-6) and the overexpression of MMP-9. In a type 2 diabetic rat model, the hydrogel accelerated full-thickness wound closure, with histological analysis revealing dense collagen deposition and enhanced angiogenesis. By synergistically integrating GelMA's MMP-9-triggered drug release with BSAMA's Auc-binding capacity, the hydrogel establishes a multifunctional platform that couples microenvironment-responsive drug delivery with anti-oxidative, anti-inflammatory, and pro-angiogenic functions, offering a promising solution for diabetic wound management.
研究领域:
生物材料
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药剂学
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伤口愈合
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糖尿病研究
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生物工程
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yuling Chen,Na Yin,Shenyao Jin,Liya Yang,Yanyun He,Ling Guo,Min Feng
Osteoarthritis is the most prevalent form of arthritis, and a leading cause of pain and long-term disability. Dysregulation of redox homeostasis is a key feature in the pathological progression of osteoarthritis that amplifies the inflammatory response, aggravates synovitis and accelerates cartilage degradation. Herein, a hemin and chitosan-mediated antioxidant gel inducing ROS conversion (hc-MAGIC) was constructed to targeting oxidative stress for osteoarthritis treatment. The optimized hc-MAGIC exhibited autonomous sol-gel-sol transition properties, which enable to be administered via intra-articular injections, prolong retention in the joint cavity, and controlled modulation of inflammation in response to ROS. Notably, with extracellular ROS fueled, hc-MAGIC could address hypoxia in the osteoarthritic joint cavity through spatiotemporally controlled generation of oxygen (O 2 ). Moreover, hc-MAGIC restored the impaired antioxidative capacity of macrophages by upregulating HO-1 on demand, resulting in suppressing excessive intracellular ROS generation. Consequently, by restoring both extracellular and intracellular redox homeostasis in osteoarthritic joints, hc-MAGIC markedly reversed the inflammatory microenvironment to support chondrogenesis, prevented cartilage degradation, and promoted cartilage repair by augmenting cartilage matrix formation. Therefore, featuring its sol-gel-sol transition properties，ROS-to-O 2 conversion, and dual-mode redox regulation, hc-MAGIC offers a potent novel therapy for on-demand modulation of inflammation in osteoarthritis.
研究领域:
药理学
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生物材料
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骨科
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炎症生物学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2018
·Vol. 14
·期 13
·1703736
·
IF 9.598
Jun-Ying Wang,Xiaoyu Mu,Yonghui Li,Fujuan Xu,Wei Long,Jiang Yang,Peixian Bian,Junchi Chen,Lufei Ouyang,Haile Liu,Yaqi Jing,Jingya Wang,Lingfang Liu,Haitao Dai,Yuanming Sun,Changlong Liu,Xiao-Dong Zhang
Catalytic nanomaterials can be used extrinsically to combat diseases associated with a surplus of reactive oxygen species (ROS). Rational design of surface morphologies and appropriate doping can substantially improve the catalytic performances. In this work, a class of hollow polyvinyl pyrrolidone-protected PtPdRh nanocubes with enhanced catalytic activities for in vivo free radical scavenging is proposed. Compared with Pt and PtPd counterparts, ternary PtPdRh nanocubes show remarkable catalytic properties of decomposing H 2 O 2 via enhanced oxygen reduction reactions. Density functional theory calculation indicates that the bond of superoxide anions breaks for the energetically favorable status of oxygen atoms on the surface of PtPdRh. Viability of cells and survival rate of animal models under exposure of high-energy γ radiation are considerably enhanced by 94% and 50% respectively after treatment of PtPdRh nanocubes. The mechanistic investigations on superoxide dismutase (SOD) activity, malondialdehyde amount, and DNA damage repair demonstrate that hollow PtPdRh nanocubes act as catalase, peroxidase, and SOD analogs to efficiently scavenge ROS.
研究领域:
纳米材料
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催化
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生物医学工程
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辐射生物学
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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 Nanomedicine
·
2022
·
IF 7.033
Yue Dai,Xuan Sha,Xiaoxi Song,Xiuli Zhang,Mengyuan Xing,Siwen Liu,Kai Xu,Jingjing Li
Purpose Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo. Methods To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo. Results The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells’ formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque. Conclusion The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.
研究领域:
纳米技术
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生物医学工程
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心血管疾病
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成像科学
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诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2019
·Vol. 19
·期 8
·1900112
·
IF 2.895
Zehong Xiang,Yanming Wang,Zhifang Ma,Zhirong Xin,Runhai Chen,Qiang Shi,Shing-Chung Wong,Jinghua Yin
Inflammation-associated thrombosis is a non-negligible source of mortalities and morbidities worldwide. To manipulate inflammation-associated coagulation, nanoparticles that contain anti-inflammatory polymer (copolyoxalate containing vanillyl alcohol, PVAX) and anti-thrombotic heparin derivative deoxycholic acid (Hep-DOCA) are prepared. The strategy takes advantage of the reducted side effects of heparin through heparin conjugation, achievement of long-term anti-inflammation by inflammation-trigged release of anti-inflammatory agents, and formation of PVAX/heparin-DOCA nanoparticles by co-self-assembly. It is demonstrated that the Hep-DOCA conjugate and PVAX are synthesized successfully; PVAX and Hep-DOCA nanodrugs (HDP) are obtained by co-assembly; the HDP nanoparticles effectively reduce the inflammation and coagulation without inducing lethal bleeding both in vivo and in vitro. The method provided here is versatile and effective, which paves new way to develop nanodrugs to treat inflammation-associated thrombosis safely.
研究领域:
药学
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纳米技术
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhiheng Luo,Jianxiong Ma,Yan Wang,Yuhan Du,Yujie Liu,Wei Zhang,Yuxiao Lai,Xinlong Ma
The management of bone defects, particularly those with irregular geometries resulting from osteoporotic fractures, remains fraught with challenges. Microspheres have emerged as a promising vehicle for tissue engineering, distinguished by their controlled release, safety, and ease of application. Various bioactive components are integrated into microspheres to improve their performance. Metal-organic frameworks, formed from metal ions interconnected by organic ligands, are increasingly utilized in tissue engineering. Specifically, magnesium-based MOFs are notable for their broad applicability; Mg 2+ ions are instrumental in bone reconstruction and repair, facilitating osteogenesis, angiogenesis, antibacterial effects, and anti-inflammatory properties. Mg-MOF was synthesized using magnesium chloride and gallic acid, and it was incorporated into gelatin microspheres to create Gel@Mg-MOF composite microspheres. Leveraging gelatin's biocompatibility, controlled release, and biodegradability, the composites' biocompatibility was evaluated through toxicity and adhesion assays. Moreover, the osteogenic and angiogenic potentials of the Gel@Mg-MOF microspheres were assessed, alongside their capacity for ROS scavenging. Results suggest that controlled Mg 2+ release from Gel@Mg-MOF microspheres promotes osteogenic activity in RBMSCs and enhances angiogenic potential in HUVECs. Additionally, the gallic acid-containing composite microspheres exhibited antioxidative properties. Collectively, the findings suggest that Gel@Mg-MOF microspheres could provide effective support for bone defect repair, with potential for clinical deployment.
研究领域:
组织工程
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生物材料
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骨再生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jianwei Wang,Xiaojia Lv,Ying Li,Haiqiang Wu,Meiwan Chen,Hua Yu,Jianwei Wu,Chenyang Li,Wei Xiong
Intestinal mucosal barrier loss is responsible for the chronic and recurrent ulcerative colitis. Myosin light chain kinase (MLCK) is a potential therapeutic target of the intestinal mucosal barrier dysfunction. Here, we developed a reactive oxygen species (ROS)-sensitive hydrogel (ATG-CS-Gel) derived from a diselenide-bridged arctigenin (ATG) and chitosan (CS) conjugate, with the aims of targeting to inflamed mucosa and modulating MLCK. Our results demonstrated that ATG-CS-Gel achieved ROS-responsive release and significantly inhibited ROS production and mitochondrial depolarization in the Caco-2 and HT-29/MTX-E12 cells under H 2 O 2 -induced stress conditions. Compared with normal tissues, orally-administrated ATG-CS-Gel preferentially adhered to the inflamed mucosa for 24 h, which was attributed to the adhesion between CS and mucin. Therapeutically, ATG-CS-Gel reduced inflammatory symptoms, accelerated intestinal mucosal healing, scavenged excessive ROS, reshaped intestinal flora, and eventually achieved much better therapeutic efficacy in DSS-induced colitis mice when compared to 5-aminosalicylic acid. Moreover, ATG-CS-Gel was demonstrated to reverse intestinal mucosal barrier loss by blocking MLCK activation and maintaining tight junction expression. In summary, this study highlights the potential of MLCK modulation in the restoration of intestinal mucosal barrier using ATG-CS-Gel. The development of ATG-CS-Gel represents a novel and promising strategy for the treatment of ulcerative colitis.
研究领域:
药理学
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胃肠病学
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生物材料科学
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炎症性肠病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Penghao Zhen,Qiaochu Jiang,Fuchao Yu,Xuan Xu,Qin Wei,Xiaoyang Liu,Xianbao Sun,Gaolin Liang,Jiayi Tong
Treatment of myocardial ischemia-reperfusion (MI/R) injury still faces the lack of clinically approved drugs. Apelin-13 is a highly promising drug candidate of MI/R injury, but hampered by its extremely short half-life in plasma. This calls for efficient and smart delivering system for Apelin-13 delivery, but has not been reported. Herein, a reactive oxygen species (ROS)-responsive hydrogelator YFF-TK-FFY is designed, which co-assembles with Apelin-13 to form the peptide hydrogel Apelin-13@Gel TK . This hydrogel responds to ROS at varying levels in the surrounding environment of MI/R and releases Apelin-13 at different rates. In an MI/R injury mouse model, Apelin-13@Gel TK rapidly releases Apelin-13 in response to the high ROS in the core area of MI/R injury, efficiently reducing cardiomyocyte apoptosis within three days. In the ROS-low border zone, Apelin-13@Gel TK provides a slow and sustained release of Apelin-13, promoting angiogenesis and lymphatic remodeling, and facilitating the resolution of inflammation in the later repair stage after MI/R injury. By offering a spatiotemporally controlled drug release in response to ROS gradients in the MI/R microenvironment, this smart hydrogel presents a promising therapeutic strategy for effective treatment of MI/R injury.
研究领域:
药理学
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心血管病学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2021
·Vol. 11
·期 11
·2875
·
IF 5.076
Yi-Mei Zhang,Meng Xia,Rui Ao,Li-Xia Gao,Yan Tang,Jiu-Hong Huang,Ya-Fei Luo,Zhong-Zhu Chen,Bo-Chu Wang,Zheng Huang
Mitochondria, as the powerhouse of most cells, are not only responsible for the generation of adenosine triphosphate (ATP) but also play a decisive role in the regulation of apoptotic cell death, especially of cancer cells. Safe potential delivery systems which can achieve organelle-targeted therapy are urgently required. In this study, for effective pancreatic cancer therapy, a novel mitochondria-targeted and ROS-triggered drug delivery nanoplatform was developed from the TPP-TK-CPI-613 (TTCI) prodrug, in which the ROS-cleave thioketal functions as a linker connecting mitochondrial targeting ligand TPP and anti-mitochondrial metabolism agent CPI-613. DSPE-PEG2000 was added as an assistant component to increase accumulation in the tumor via the EPR effect. This new nanoplatform showed effective mitochondrial targeting, ROS-cleaving capability, and robust therapeutic performances. With active mitochondrial targeting, the formulated nanoparticles (TTCINPs) demonstrate much higher accumulation in mitochondria, facilitating the targeted delivery of CPI-613 to its acting site. The results of in vitro antitumor activity and cell apoptosis revealed that the IC50values ofTTCINPs in three types of pancreatic cancer cells were around 20~30 µM, which was far lower than those of CPI-613 (200 µM); 50 µMTTCINPs showed an increase in apoptosis of up to 97.3% in BxPC3 cells. Therefore, this mitochondria-targeted prodrug nanoparticle platform provides a potential strategy for developing safe, targeting and efficient drug delivery systems for pancreatic cancer therapy.Keywords:mitochondria-targeting;ROS-responsive;drug delivery;nanoparticles;pancreatic cancer therapy;CPI-613
研究领域:
癌症治疗
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药学科学
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纳米技术
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2025
·
IF 2.9
Leina Jia,Xiaoning Meng,Yu Ma,Jinyu Luo,Xiaoqi Luo,Huifang Yang,Jian Zhou
Cypermethrin (CYP, IUPAC name: [cyano-(3-phenoxyphenyl)methyl] 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate), a type II pyrethroid insecticide, is suggested to have potential adverse effects on human endocrine, immune, and neurotoxic systems. Objectives: In this study, we aimed to investigate whether CYP causes oxidative stress and pyroptosis in thyroid follicle epithelial cells through the activation of the ROS-NFκB-NLRP3 pathway, thereby causing inflammatory responses. Methods: Nthy-ori 3-1 cells were used as an in vitro model and exposed to CYP at different doses (0, 100, 200, 400, 800, and 1600 μmol/L) for 24 h. Results: CYP treatment enhanced oxidative damage in Nthy-ori 3-1 cells, characterized by cellular crumpling, indistinct borders, increased cellular gaps, appearance of intercellular grease droplets, and increased pyroptosis. Subsequent treatment with the caspase-1 inhibitor VX-765 enhanced cell viability in the VX-765+CYP group, improving cell morphology, reducing pyroptotic vesicles, suppressing oxidative stress, and downregulating Interleukin-18(IL-18) (an inflammatory factor) level. Conclusion: The results demonstrate that CYP induces pyroptosis in Nthy-ori 3-1 cells through activation of the reactive oxygen species (ROS)-NF-κB-NLRP3 pathway.
研究领域:
毒理学
·
内分泌学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Wenjia Xie,Yuxuan Wang,Jicenyuan Wu,Xu Wang,Jiaxin Wu,Bin Cheng,Hao Feng,Xinxu Huang,Xinting Cheng,Junyu Chen,Qianbing Wan,Jian Wang,Xibo Pei
Diabetic periodontitis is characterized by persistent and aggravated inflammation, largely driven by a reactive oxygen species (ROS) vicious loop in M1 macrophages driven by mitochondrial dysfunction. To disrupt this pathogenic cascade, we developed hierarchically targeted polymeric nanoparticles (MPPT NPs) by conjugating the tuftsin peptide for selective uptake by M1 macrophages and loading mitoquinone mesylate (MitoQ) to restore mitochondrial function after mitochondrial localization. For local retention and responsive drug release, MPPT NPs were incorporated into a ROS-responsive hydrogel (MTP hydrogel) constructed by cross-linking poly(vinyl alcohol) (PVA) with a ROS-cleavable linker (N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA)). This constructed platform not only enabled the on-demand release of MPPT NPs but also provided additional ROS-scavenging ability. In vitro studies demonstrated that MTTP NPs effectively repaired oxidatively damaged mitochondria and suppressed NLRP3 inflammasome priming and activation. MTP hydrogel platform reduced pro-inflammatory cytokine release and rescued inflammation-induced osteogenic impairment. In a diabetic periodontitis rat model, local administration of the MTP hydrogel significantly attenuated periodontal tissue destruction and promoted alveolar bone regeneration, achieving BV/TV 1.5 times that of previous reports. Collectively, this hierarchically targeted and ROS-responsive platform disrupts the ROS vicious loop in M1 macrophages by repairing damaged mitochondria, offering a promising therapeutic strategy for the management of diabetic periodontitis.
研究领域:
纳米医学
·
牙科
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免疫学
·
活性氧信号通路
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生物材料
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炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Huiquan Yang,Wenbin Chen,Jun Ma,Jing Zhao,Dongdong Li,Yuyu Cao,Peidang Liu
Background The synergistic effect of nanomaterials and chemotherapeutics provides a novel strategy for the treatment of tumors. Silver nanotriangles (AgNTs) exhibited some unique properties in nanomedicine. Studies on the synergy of silver-based nanomaterials and anti-tumor drugs against gliomas are rare.Materials and Methods Chitosan-coated AgNTs were prepared, followed by characterization using transmission electron microscopy, ultraviolet-visible spectroscopy and X-ray diffraction. The anti-glioma effect of cyclophosphamide (CTX), 5-fluorouracil (5-FU), oxaliplatin (OXA), doxorubicin (DOX) or gemcitabine (GEM) combined with AgNTs in different glioma cell lines (U87, U251 and C6) was assessed by the MTT assay to screen out a drug with the most broad-spectrum and strongest synergistic anti-glioma activity. The intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) and cell apoptosis were detected by flow cytometry. The possible underlying mechanisms of the synergy were further investigated with ROS scavenger and specific inhibitors of C-jun N-terminal kinase (JNK), p38 and extracellular signal-regulated kinase 1/2 pathways.Results The synthesized AgNTs were mainly triangular and truncated triangular with an average edge length of 125 nm. A synergistic anti-glioma effect of AgNTs combined with CTX was not observed, and the synergism between AgNTs and 5-FU was cell type-specific. AgNTs combined with OXA, DOX or GEM displayed synergistic effects in various glioma cell lines, and the combination of AgNTs and GEM showed the strongest synergistic activity. A decrease in cell viability, loss of the MMP and an increase in apoptosis rate induced by this synergy could be significantly attenuated by the ROS scavenger N-acetylcysteine and JNK inhibitor SP600125.Conclusion Our results suggested that the combination of AgNTs and GEM possessed broad-spectrum and potent synergistic anti-glioma activity, resulting from cell apoptosis mediated by a ROS-dependent mitochondrial pathway in which JNK might be involved.
研究领域:
纳米医学
·
肿瘤学
·
细胞生物学
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药理学
✓ 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）