Materials Horizons
·
2024
·
IF 12.2
Weikai Chen,Shihao Sheng,Kai Tan,Sicheng Wang,Xiang Wu,Jiayi Yang,Yan Hu,Liehu Cao,Ke Xu,Fengjin Zhou,Jiacan Su,Qin Zhang,Lei Yang
The degradability of hydrogels plays a pivotal role in bone regeneration, yet its precise effects on the bone repair process remain poorly understood. Traditional studies have been limited by the use of hydrogels with insufficient variation in degradation properties for thorough comparative analysis. Addressing this gap, our study introduces the development of matrix metalloproteinase (MMP)-responsive hydrogels engineered with a tunable degradation rate, specifically designed for bone regeneration applications. These innovative hydrogels are synthesized by integrating MMP-sensitive peptides, which exhibit chirality-transferred amino acids, with norbornene (NB)-modified 8-arm polyethylene glycol (PEG) macromers to form the hydrogel network. The degradation behavior of these hydrogels is manipulated through the chirality of the incorporated peptides, resulting in the classification into L, LD, and D hydrogels. Remarkably, the L hydrogel variant shows a significantly enhanced degradation rate, both in vitro and in vivo, which in turn fosters bone regeneration by promoting cell migration and upregulating osteogenic gene expression. This research highlights the fundamental role of hydrogel degradability in bone repair and lays the groundwork for the advancement of degradable hydrogel technologies for bone regeneration, offering new insights and potential for future biomaterials development.
研究领域:
生物材料
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组织工程
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生物医学工程
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Wenming Ai,Yingcui Bu,Houshi Huang,Junjun Wang,Mengjuan Ren,Yu Deng,Yicai Zhu,Sen Wang,Zhi-Peng Yu,Hongping Zhou
Mitochondrial membrane potential (MMP) and sulfur dioxide (SO2) significantly affect the mitochondrial state. In this work, TC-2 and TC-8 were constructed through side-chain engineering, in which TC-2 bearing the poorer hydrophobicity could localize on mitochondria better. Interestingly, short-wave emission was captured due to the sensitive response of TC-2 to SO2 (LOD = 13.8 nM). Meanwhile, the probe could bind with DNA, presenting enhanced long-wave emission. Encouragingly, TC-2 could migrate from mitochondria to the nucleus when MMP was decreased, accompanied by the increase of fluorescence lifetime (9-fold). Hence, TC-2 could be used for dual-channel monitoring of mitochondrial SO2 and MMP, which showed a completely different pathway from the commercial MMP detectors JC-1/JC-10. The cellular experiments showed that MMP was gradually decreased due to reactive oxygen species-triggered oxidative stress, and the SO2 level was up-regulated simultaneously. Overall, this work proposed a new method to investigate and diagnose the mitochondrial-related diseases.
研究领域:
生物技术
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细胞生物学
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分析化学
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DOI
PubMed
高影响因子
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
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 9
·1410-1417
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IF 7.571
Baofu Ma,Jianyu Han,Kun Zhang,Qike Jiang,Zhigang Sui,Zhixin Zhang,Baofeng Zhao,Zhen Liang,Lihua Zhang,Yukui Zhang
Nanozymes have great potential applications in tumor treatment due to their good stability, high biocompatibility, easy preparation and versatility. However, it remains a challenge to design highly active nanozymes with tumor cell targeting. Herein, three nanoceria structures (nanoceria-rod; nanoceria polyhedra, abbreviated as nanoceria-poly.; and nanoceria-cube) with different surface oxygen vacancy concentrations are designed. Among them, nanoceria-rod shows the highest enzyme activity and tumor cell toxicity because of its highest concentration of oxygen vacancies on the surface. Further study shows that nanoceria-rod can selectively enter tumor cells because nanoceria-rod with a suitable isoelectric point (IEP) remains positively charged in the acidic microenvironment of the tumor but negatively charged in the physiological microenvironment of normal cells. Nanoceria-rod distributes in lysosomes and phagosomes to produce reactive oxygen species (ROS) in tumor cells. Finally, the mitochondrial membrane potential (MMP) was reduced, which caused cell apoptosis. This study provides an interesting new tumor-targeting therapy method, which could also be extended to other drug nanocarriers and diagnostic imaging nanomaterials for tumors.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2023
·Vol. 75
·期 4
·502-514
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IF 3.3
Zhou Nan,Yong Suyun,Shi Xianpeng,Zhang Peng,Wang Jianhua
ObjectivesReactive oxygen species (ROS) are involved in the structural remodelling of vascular segments and vascular beds. We identified a new imperatorin derivative, OW1, which has significant effects on vasodilation and inhibits vascular remodelling in hypertensive rats. In this study, we investigated whether OW1 inhibits vascular cell proliferation and migration by attenuating Nox1-ROS signalling.MethodsVascular smooth muscle cells (VSMCs) were treated with OW1 (1, 3 and 10 µmol/L) for 24 h incubation, and it has been analysed for proliferation and peroxidation levels. Moreover, the mRNA and protein levels of nicotinamide adenine dinucleotide phosphate oxidase (Noxs) were measured by RT-PCR and western blot. Furthermore, Nox1-ROS-MAPK/MMP mediated cell proliferation was detected by western blot.Key findingsAng II-induced increases in the levels of peroxidation and Noxs in VSMCs were also inhibited by OW1. OW1 attenuates cell proliferation and migration through the MAPK pathway and MMPs. OW1 treatment had no significant effects on cell migration, ROS levels, or the expression of phosphorylated MAPKs in VSMCs when Nox1 was knocked down. OW1 reduced ROS levels and expression of phosphorylated MAPKs in NIH3T3 cells with a Nox1 overexpression plasmid.ConclusionOW1 may inhibit vascular remodelling by downregulating the Nox1-ROS-MAPK/MMP signalling pathway.
研究领域:
药理学
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心血管生物学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 11
·1516-1521
·
IF 2.378
Fujuan Luan,Zuhong Yu,Ling Yin,Xia Leng,Yuxue Shi,Jie Wang,Haibin Shi,Weichang Chen
Matrix metalloproteinase-2 (MMP-2) plays an important role in tumorigenesis and metastasis of gastric cancer. Therefore, specific and sensitive detection of MMP-2 is of great significance for clinical diagnosis and therapeutic evaluation of gastric cancer. Herein, we developed a new approach for accurate detection of MMP-2 activity both in gastric cancer cells and clinical tissues using a fluorescent probe Dab-PLGVRGY-FITC. The capability of the probe for detecting MMP-2 was systematically evaluated in gastric cancer MGC-803 cells and clinical gastric cancer tissues. Around 40-fold fluorescence enhancement at a wavelength of 520 nm was determined for the assays of the probe with recombinant MMP-2. The detection limit of MMP-2 was as low as 42 ng mL−1. Strong fluorescence signals were detected in MGC-803 cells and mouse gastric cancer tissues. Fluorescence signal enhancements of 11 clinical gastric cancer tissue lysates were 5.8 ∼ 9 times (7.53 ± 0.77 on average) higher than those from gastritis patients. This probe could be potentially used for early diagnosis of gastric cancer in clinics.
研究领域:
肿瘤学
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生物医学工程
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临床诊断
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DOI
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
·
2018
·Vol. 120
·期 6
·9648-9655
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IF 2.959
Chaozhi Ma,Liyuan Zou,Yu Xia,Yijun Tu,Daquan Xue,Yanfang Yang,Dan Liu,Yanwen Liu,Hezhen Wu,Hanxiong Dan,Pengtao You
Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule-1 (ICAM-1), phosphorylation of p65 (p-p65), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)-4, IL-5, and IL-17 in serum and BALF were significantly decreased, and interferon-γ (IFN-γ) and IL-10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM-1, p-p65, MMP-9, and TIMP-1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA-induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.
研究领域:
药理学
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免疫学
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呼吸医学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Liu Ying,Tang Rui,Cao Yuting,Wu Nianhong,Qin Qiaoxi,Chen Yuanyuan,Wei Xi,Ren Jianli,Sun Yang,Zhou Hong,Zhou Yang,Li Pan
Background Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment. Results Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis. Conclusions Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings. Graphical Abstract
研究领域:
肿瘤学
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Chengbai Dai,Cheng Chen,Jun Zhu,Minghao Chao,Hanrong Yan,Pengjin Wei,Ming Guan,Bin Pan,Fenglei Gao,Rongze Tang
ZCM2 reprograms redox–inflammatory coupling by activating Nrf2/HO-1 signaling and suppressing NF-κB–driven responses in macrophages. • ZCM2 disrupts macrophage-mediated matrix degradation via downregulation of MMP-9, mitigating pathological bone resorption. • Calcium ion release from ZCM2 instructs osteogenic commitment through activation of the RUNX2-centered transcriptional network. • ZCM2 achieves immune modulation–coupled bone regeneration, enabling systemic restoration of bone homeostasis in osteoporosis. Osteoporosis is a systemic skeletal disorder characterized by bone loss and microstructural deterioration, and its pathogenesis is closely associated with dysregulation of the bone marrow immune microenvironment. In this study, bioinformatic analysis first revealed significant oxidative stress and mitochondrial metabolic dysfunction in macrophages within the osteoporotic microenvironment. Based on this, we constructed a biomimetic nanoplatform (ZCM2) composed of ZIF-8@CaCO 3 core–shell nanoparticles camouflaged with M2 macrophage membranes, designed to achieve comprehensive osteoporosis therapy through a triple synergistic mechanism: the ZIF-8 core scavenges reactive oxygen species to exert antioxidant and anti-inflammatory effects, inhibits MMP-9 secretion to reduce pathological bone resorption, and the CaCO 3 shell releases calcium ions to promote osteogenic differentiation. ZCM2 exhibited favorable biosafety, high cellular uptake efficiency, and excellent bone-targeting capability. Mechanistic studies demonstrated that ZCM2 upregulates the expression of Nrf2 and HO-1, downregulates the expression of NF-κB p65, and significantly reduces the secretion of matrix metalloproteinase-9 (MMP-9) by macrophages, thereby attenuating bone resorption. Meanwhile, calcium ions released from the CaCO 3 shell activate the RUNX2/OSX/OPN signaling axis, promoting osteogenic differentiation of bone marrow mesenchymal stem cells. In an ovariectomized mouse model of osteoporosis, ZCM2 markedly improved bone microarchitecture, promoted new bone formation, and effectively inhibited bone resorption activity. Collectively, this biomimetic nanoplatform integrates anti-inflammatory, anti-resorptive, and pro-osteogenic functions, offering a multifaceted synergistic therapeutic strategy for osteoporosis. M2 macrophage membrane–biomimetic nanoparticles activates the Nrf2/HO-1 antioxidant pathway in macrophages, thereby inhibiting NF-κB activation and MMP-9 secretion, which suppresses pathological bone resorption. Download: Download high-res image (327KB) Download: Download full-size image
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DOI
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-15
·
IF 5.1
Fan Zhan,Xu Yilun,Lu Yafang,Li Xinlin,Xu Mengli,Liu Jinxin,Cai Zhenzhen,Liu Jiayang,Su Jingping,Wang Jialu,Luo Qingming,Zhang Zhihong,Liu Zheng
The excessive accumulation of neutrophils within the epidermis is a significant hallmark of cutaneous diseases; however, the mechanisms governing neutrophil transepidermal migration (NTEM) remain inadequately understood. In this study, we develop trichromatic-fluorescence-labeled chimeric mice by utilizing Cx3cr1 GFP/+ Lyz2 RFP/+ mice as bone marrow donors and Krt14 YFP/+ mice as recipients. This approach enables us to visualize the process of NTEM and the crosstalk between neutrophils and monocytes in a murine model of irritant contact dermatitis (ICD). Intravital imaging reveals a preferential transmigration of neutrophils through hair follicle (HF), where dermal neutrophils exhibit limited mobility and interact with dermal monocytes. Notably, 18 h following hapten exposure, dermal neutrophils continuously migrate toward HF regions and form clusters within 3 h. Importantly, MMP-9 is identified as essential for the NTEM process; the depletion of dermal monocytes results in a significant reduction of MMP-9 expression in the skin and inhibits the NTEM process in ICD. Mechanistically, dermal monocytes are found to be a crucial source of the cytokines TNF-α and CXCL2, which promote the upregulation of MMP-9 in neutrophils. Therefore, our results highlight HF regions as crucial gateways for dermal monocyte-modulated NTEM and provide visual insights into the crosstalk between neutrophils and monocytes in inflammatory skin disorders.
研究领域:
免疫学
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皮肤病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-14
·
IF 10.435
Yang Yuming,Han Yu,Sun Qiuyang,Cheng Jin,Yue Caixia,Liu Yanlei,Song Jie,Jin Weilin,Ding Xianting,de la Fuente Jesús M.,Ni Jian,Wang Xiaoqiang,Cui Daxiang
Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.Conclusion sThe development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.
研究领域:
纳米技术
·
肿瘤学
·
药学
·
分子医学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 26
·4314-4325
·
IF 4.776
Tao Liu,Shaohua Chen,Siyi Zhang,Xidong Wu,Peina Wu,Beiping Miao,Xiang Cai
Transferrin-functionalized chitosan-graft-poly(L-lysine) dendrons (CS–PLLD–Tf) were synthesized in this work and then used to deliver the MMP-9 shRNA plasmid to HNE-1 cells for gene therapy. The obtained CS–PLLD–Tf displayed excellent gene transfection in vitro, verifying the strategy of constructing a high-efficiency gene carrier by conjugating the multiple low generation PLLDs to one molecule of CS to form a copolymer. Particularly, CS–PLLD–Tf showed much higher gene transfection efficiency than PEI-25k and CS–PLLD in the presence of serum, and more than 40% HNE-1 cells were transfected. This result led to an obvious decrease in MMP-9 protein expression and the apoptosis of HNE-1 cells as well as inhibition of the growth and invasion of HNE-1 tumors. The in vivo anti-tumor assay showed that CS–PLLD–Tf delivered the MMP-9 plasmid effectively and the tumor volume decreased more than 77% compared with the PBS control group. Moreover, CS–PLLD–Tf displayed higher bioavailability and good biocompatibility such as lower cytotoxicity, excellent blood compatibility and non-toxicity to organs, suggesting a potential application in gene therapy of tumors.
研究领域:
癌症研究
·
基因治疗
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生物医学工程
·
药剂学
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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）