ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2020
·
IF 3.391
Jia-Yu Shi,Hai-Yan Pan,Kun Liu,Min Pan,Guo-Jun Si
Background Our previous research revealed that trypsin is abundantly expressed in atherosclerotic plaques and its distribution overlaps with that of matrix metalloproteinase-9 (MMP-9). This study was performed to explore the possible roles of trypsin in vulnerable atherosclerotic plaque formation. Methods and results Twenty-four rabbits were randomly assigned to a normal (control) group, an atherosclerosis (experimental) group and a trypsin inhibitor (aprotinin) group. In the 13th feeding week, the aprotinin group was treated with 5 mg/kg/day aprotinin via ear vein for 4 weeks. At the end of the 16th week, coronary arterial and aortic expression of trypsin, proteinase-activated receptor-2 (PAR-2), activated MMP-9, and pro-inflammatory cytokines were significantly greater in the experimental group than in the control group. Aprotinin decreased trypsin expression and activation in plaques, blocked PAR-2 and MMP-9 activation, and decreased cytokine expression; it also increased fibrous cap thickness, decreased the intima-media thickness and intimal/medial ratio, thus significantly ameliorating plaque vulnerability. Upregulated trypsin, MMP-9 and PAR-2 were also found in coronary intimal atherosclerotic plaques of patients undergoing coronary artery bypass grafting. Conclusions Ectopic trypsin was significantly upregulated in atherosclerotic plaques, which increased pro-inflammatory cytokine levels by activating PAR-2 and promoted plaque instability by activating proMMP-9, thereby promoting atherosclerosis and plaque vulnerability. In addition, the high trypsin expression in human coronary intimal atherosclerotic plaques suggests that targeting trypsin may be a new strategy for acute coronary syndrome prevention.
研究领域:
心脏病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Wu Zhen,Zhang Peng,Yue Jie,Wang Qingshan,Zhuang Peipei,Jehan Shah,Fan Liyuan,Xue Jiarun,Zhou Wenhu,Wang Haiyang
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier’s intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy.Graphical Abstract
研究领域:
纳米技术
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基因治疗
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血管生物学
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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
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2013
·
IF 3.848
Lin-Hui Zhang,Yong-Liang Jia,Xi-Xi Lin,Hong-Quan Zhang,Xin-Wei Dong,Jun-Ming Zhao,Jian Shen,Hui-Juan Shen,Fen-fen Li,Xiao-Feng Yan,Wei Li,Yu-Qing Zhao,Qiang-Min Xie
Background Ginseng is a traditional Chinese herb that has been used for thousands of years. In the present study, effects and mechanisms of AD-1 were evaluated for its development as a novel anti-lung cancer drug. Methods The cytotoxic activity was evaluated by MTT assay. Flow cytometry was employed to detect cell cycle, apoptosis and ROS. Western blot and immunohistochemistry were used to analyze signaling pathways. Lung cancer xenograft models were established by subcutaneous implantation of A549 or H292 cells into nude mice. Results AD-1 concentration-dependently reduces lung cancer cell viability without affecting normal human lung epithelial cell viability. In A549 and H292 lung cancer cells, AD-1 induces G 0 /G 1 cell cycle arrest, apoptosis and ROS production. The apoptosis can be attenuated by a ROS scavenger — N-acetylcysteine (NAC). In addition, AD-1 up-regulates the expression of p38 and ERK phosphorylation. Addition of a p38 inhibitor SB203580, suppresses the AD-1-induced decrease in cell viability. Furthermore, genetic silencing of p38 attenuates the expression of p38 and decreases the AD-1-induced apoptosis. Treatment with NAC reduces AD-1-induced p38 phosphorylation, which indicates that ROS generation is involved in the AD-1-induced p38 activation. In mice, oral administration of AD-1 (10–40 mg/kg) dose-dependently inhibited the growth of xenograft tumors without affecting body weight and decreases the expression of VEGF, MMP-9 and CD34 in tumor tissue. TUNEL staining confirms that the tumors from AD-1 treated mice exhibit a markedly higher apoptotic index. Conclusions and general significance These data support development of AD-1 as a potential agent for lung cancer therapy.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-14
·
IF 9.429
Deng Bo,Ma Bing,Ma Yingying,Cao Pei,Leng Xigang,Huang Pengyu,Zhao Yuanyuan,Ji Tianjiao,Lu Xueguang,Liu Lanxia
Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8 + and CD4 + T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect. Graphical Abstract
研究领域:
癌症治疗
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药物递送系统
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免疫疗法
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纳米医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
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IF 26.8
Yu Zhang,Wu Yang,Wei Xiong,Yu Chen,Pengzhen Zhuang,Haoran Wang,Diana M. Toivola,Yawei Du,Hongbo Zhang,Wenguo Cui
The positive feedback circuit between the complement system and inflammatory immune responses maps the malignant progression of chronic joint inflammation. Prolonged dysregulation of the immune microenvironment in rheumatoid arthritis (RA) further exacerbates sustained complement activation, thereby establishing a vicious cycle. In this study, MMP-9-responsive, injectable micro-nano geneplexes (C5ASO@HAP-CL-TIMP@HMs) are developed for on-demand regulation of complement component C5, aiming to disrupt this pathological circuit. C5 antisense oligonucleotides (C5ASO) are loaded into cationic liposomes, which are subsequently encapsulated within hyaluronic acid microspheres via click chemistry. In vitro, these geneplexes effectively block abnormal C5 activation in RA synoviocytes, restore macrophage polarization balance, reduce pro-inflammatory cytokine levels and immune complex precursor molecules, and upregulate anti-inflammatory mediators. In an adjuvant-induced arthritis rat model, they significantly alleviate joint swelling and cartilage degradation and suppress inflammatory responses, further highlighting the therapeutic potential of geneplexes in dismantling the complement-inflammation circuit. In summary, the development of micro-nano geneplexes capable of precisely disrupting the complement-inflammatory circuit in RA offers a promising new perspective for the targeted treatment of chronic joint inflammation.
研究领域:
免疫学
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纳米医学
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风湿病学
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基因递送
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炎症性疾病
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2021
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IF 6.4
Linming Li,Yan Chen,Qingpeng Wang,Zuojie Li,Zhifang Liu,Xuewen Hua,Jun Han,Chunxiao Chang,Zhengping Wang,Dacheng Li
Background Platinum(IV) complexes with inflammation inhibitory properties are much favored in improving antitumor activities. Nanodrug-delivery system as a preferable measure for antitumor therapy are widely explored in platinum(IV) drug delivery. Purpose The aim for this study was to develop novel bovine serum albumin (BSA) nanoparticles (NPs) based on naproxen platinum(IV) complexes to display a synergistic antitumor mechanism targeting cyclooxygenase-2 (COX-2), metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS). Methods Herein, we reported the preparation of two BSA NPs of naproxen platinum(IV) complexes, and their antitumor activities were investigated in vitro and in vivo. Results Both NPs possessed relatively uniform size and good stability for 30 days in aqueous solution. They exhibited prominent antitumor activities in vitro, and showed great potential in reversing drug resistance. Furthermore, these two NPs played superior tumor growth suppression in vivo in contrast to the free compounds, which were comparable to that of cisplatin and oxaliplatin, but induced lower toxic influences than platinum(II) drugs especially to spleen and liver. Moreover, the naproxen platinum(IV) NPs could decrease tumor inflammation targeting COX-2, MMP-9 and iNOs, and decreasing NO production, which would be in favor of enhancing the antitumor competence, and reducing toxicity. Conclusion Taken together, BSA NPs of naproxen platinum(IV) complexes demonstrated a powerful antitumor efficacy in vitro and in vivo. The platinum(IV) NPs with inflammation inhibitory competence targeting multiple enzymes reported in this work afford a new strategy for the development of antitumor therapy to overcome drawbacks of clinical platinum(II) drugs.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2020
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IF 5.162
Biyun Lan,Junfeng Wu,Na Li,Chenglin Pan,Li Yan,Chuan Yang,Liming Zhang,Liqun Yang,Meng Ren
Gene vectors are important for successful siRNA delivery. Four types of hyperbranched cationic polysaccharide derivatives (HCP) were synthesized by conjuncting 1,2-ethylenediamine (EDA) and diethylenetriamine (DETA) with glycogen or amylopectin respectively and named as G-EDA, G-DETA, A-EDA and A-DETA. The efficiency and safety of these HCPs to deliver siRNA were explored in vitro and in vivo . Our results showed that HCPs could form complexes with siRNA. All HCP/siRNA exhibited negligible cytotoxicity. Compared with A-EDA and A-DETA, G-EDA and G-DETA could carry much more siRNA into cells and then escape from endosomes. The delivery of MMP-9 siRNA (siMMP-9) by G-EDA and G-DETA significantly inhibited MMP-9 in HaCaT cells. Wound models in diabetic rats demonstrated that treatment of G-EDA/siMMP-9 could potently knock down MMP-9 of skin wound tissues and then enhanced wound healing. In summary, this study provided an effective and safe approach for siRNA delivery in vitro and in vivo .
研究领域:
药学科学
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生物技术
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伤口愈合
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糖尿病研究
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纳米技术
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基因治疗
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产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
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2022
·
IF 5.545
Tong Shanshi,Yu Zhilong,Yin Fang,Yang Qilin,Chu Juhang,Huang Luyao,Gao Wenxue,Qian Mingping
Pancreatic cancer (PC) is one of the deadliest gastrointestinal malignancies. Advances in molecular biology and surgery have significantly improved survival rates for other tumors in recent decades, but clinical outcomes for PC remained relatively unchanged. Chemodynamic therapy (CDT) and Photothermal therapy (PTT) represent an efficient and relatively safe cancer treatment modality. Here, we synthesized Mn-doped Prussian blue nanoparticles (MnPB NPs) through a simple and mild method, which have a high loading capacity for drugs and excellent CDT/PTT effect. Cell line experiments in vitro and animal experiments in vivo proved the safety of MnPB NPs. We stimulated the PC cells with MnPB NPs and performed transwell migration assays. The migration of PC cells was reduced company with the decrease of two classical proteins: matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Moreover, MnPB NPs induced ferroptosis, which mediated the MAPK pathway and achieved tumor elimination in nude mice. This effective and safe strategy controlled by irradiation represents a promising strategy for pancreatic cancer.
研究领域:
肿瘤学
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纳米技术
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2023
·
IF 12.6
Liangliang Xiang,Wenting Cheng,Jiakang Zhang,Xiaoyue Li,Adeel Khan,Yongxiang Yi,Jinlong Li
Matrix metalloproteinase-9 (MMP-9) has been implicated in various tumor cell invasions and metastases. In light of the limitations of traditional methods for MMP-9 detection, we have constructed a novel biosensor depending on cucurbit[8]uril (CB[8]) -mediated host-guest interactions and a sacrificial iron metal-organic framework (FeMOF). Herein, MMP9-specific peptides modified on the gold bare electrode are bonded to the [email protected] @peptide complex through CB[8] addition. The connection between MMP9-specific peptides and signal peptides via CB[8] provides stability as well as enables the immobilization of FeMOF on the electrode surface . When Fe 3+ from the FeMOF interacts with electrochemical buffer K 4 Fe(CN) 6 , Prussian blue will be generated on the gold electrode surface, and a significantly enlarged current response can be detected. However, in the presence of MMP-9, their peptide substrates are specifically cleaved at the site between serine (S) and Leucine (L), which causes an abrupt decrease in the electrochemical signal. The change of signal can reflect MMP-9 concentration. This sensor can reach an ultrahigh sensitivity with a wide detection range of 0.5 pg⋅mL −1 to 500 ng⋅mL −1 and a low detection limit of 1.30 pg⋅mL −1 . Importantly, this sensor is very simple, relying solely on self-sacrificial label of FeMOF, rather than complex functional materials. Additionally, it has been well used in serum samples, showing attractive potential for practical applications.
研究领域:
生物化学
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分析化学
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生物传感器
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Ying Li,Xin Zhang,Dan He,Zhijie Ma,Ke Xue,Haiyan Li
Diabetic chronic wounds are difficult to heal because of the presence of excessive inflammation and high overexpression of matrix metalloproteinase-9 (MMP-9), which greatly affects the quality of life of patients with diabetes and increases the risk of death. Thus, the regulation of excessive inflammation and inhibition of MMP-9 overexpression are effective strategies to improve diabetic wound healing. The present study is the first to demonstrate that ion products of 45S5 Bioglass® (BG) can work with small interfering RNA of MMP9 (MMP9-siRNA) to reduce MMP-9 expression in tissue-forming cells and enhance the synthesis of extracellular matrix proteins (ECMs). Specifically, the BG ionic products can stimulate macrophages to convert to M2 phenotype, thereby creating a proregenerative inflammation microenvironment to indirectly suppress the expression of MMP-9 in tissue-forming cells. Chitosan nanoparticles encapsulating MMP9-siRNA (MMP9-siNP) can directly lower MMP-9 expression in tissue-forming cells. In addition, BG ionic products can promote the vascularization of endothelial cells and ECM protein synthesis by fibroblasts. Thus, injectable BG/sodium alginate (BG/SA) hydrogels loaded with MMP9-siNP can significantly accelerate the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen synthesis , and enhancing angiogenesis in the wounds, thereby demonstrating their great application potential in treating diabetic chronic wounds. Statement of significance Excessive inflammation and high overexpression of MMP-9 have been considered as factors that severely hinder the healing process of diabetic chronic wounds. Effective strategies are required for the regulation of excessive inflammation and inhibition of MMP-9 overexpression to enhance diabetic wound healing. In the present work, an injectable bioglass/sodium alginate (BG/SA) hydrogel loaded with MMP9-siNP was developed; this hydrogel significantly accelerated the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen accumulation, and enhancing angiogenesis in the wounds. Thus, the BG/SA hydrogel loaded with MMP9-siNP has great potential for use in healing of diabetic chronic wounds.
研究领域:
生物材料
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伤口愈合
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糖尿病
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组织工程
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纳米技术
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Wang Zhiwei,Sun Lingshun,Wang Weixing,Wang Zheng,Shi Ge,Dai Honglian,Yu Aixi
Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix (ECM) and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsions (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit matrix metalloproteinases (MMPs), increase angiogenesis, and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties, and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition, and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis, and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance, and excellent mechanical properties.
研究领域:
材料科学
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生物医学工程
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药剂学
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伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 45
·7141-7151
·
IF 5.047
Jun Zhang,Tiantian Zuo,Xiao Liang,Yingxin Xu,Yifan Yang,Tianxu Fang,Jing Li,Daijie Chen,Qi Shen
Triple-negative breast cancer (TNBC) is characterized by a high metastatic rate, which can seriously threaten women's health. ROS play an important role in tumor development and metastasis. Excessive ROS can induce tumor cell apoptosis and inhibit tumor cell metastasis. This study investigated Fenton-reaction-stimulative nanoparticles (P@P/H NPs) containing ROS-responsive molecular switches for antitumor metastasis by amplifying the ROS and activating the cascade biological reaction of ROS in tumor cells. Spheroidal P@P/H NPs exhibited a uniform size of 68.18 ± 0.29 nm, high drug cumulative release of 97.59% in response to H2O2 at 24 h, and satisfactory cytotoxicity with the IC50 value of 0.50 ± 0.02 μg mL−1. The markedly elevated ROS level caused by P@P/H NPs generated an evident antitumor metastasis effect in vitro by facilitating the expressions of cytochrome c, caspase-9, and caspase-3 and blocking that of matrix metalloprotein 9 (MMP-9). Moreover, P@P/H NPs engendered an excellent tumor inhibition rate of 56.37% and antitumor metastasis effect in vivo. Therefore, P@P/H NPs could respond to H2O2 in tumor cells to rapidly disassemble and further increase the ROS to induce antitumor metastasis via the Fenton reaction.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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药学
✓ 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）