Frontiers in Pharmacology
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2026
·
IF 5.4
Qinghua Lan,Leyi Zhang,Yu Wang,Haici Lan,Qianqian Hu,Xiayan Zhang,Songmei Luo,Yanyan Xu
Introduction Psoriasis is an autoimmune disease characterized primarily by chronic inflammation, with suboptimal clinical therapeutic outcomes. Quercetin, a bio-safe plant secondary metabolite, exerts anti‐inflammatory effects by modulating multiple signaling pathways and holds promise as a therapeutic candidate for psoriasis. Methods Our preliminary studies demonstrated that silk protein (SF) derived from silkworm cocoons exhibits excellent biocompatibility and can form hydrogels, serving as an ideal drug carrier for skin applications. We loaded quercetin into the SF hydrogel system and systematically investigated the therapeutic efficacy of this composite formulation (QSF) against imiquimod-induced psoriasis models through in vitro and in vivo experiments. Results The hydrogel exhibited desirable enzyme-responsive properties. When exposed to an in vitro microenvironment containing 10 nM MMP‐9, the hydrogel network rapidly disintegrated, achieving a cumulative quercetin release of 58.26% ± 7.64% within 24 h. The enriched quercetin in lesion tissues markedly reduced the positive expression levels of IL‐17, TNF‐α, and IL‐1β, with inhibition rates of 32.14%, 20.25%, and 33.71%, respectively, which effectively interrupted the inflammatory cascade and obviously alleviated skin desquamation and pruritus. Discussion Collectively, the fabricated QSF hydrogel presents anti‐inflammatory and symptomatic relief effects, providing a feasible strategy and experimental basis for the development of novel topical preparations for psoriasis treatment.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-17
·
IF 10.435
Lan Biyun,Zhang Liming,Yang Liqun,Wu Junfeng,Li Na,Pan Chenglin,Wang Xiaoyi,Zeng Lexiang,Yan Li,Yang Chuan,Ren Meng
AbstractExcessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases.
研究领域:
药学
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生物医学工程
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伤口愈合
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糖尿病
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高影响因子
Journal of Pharmaceutical Innovation
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2022
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IF 2.538
Sun Yu
Purpose In this study, we fabricated a nanoplatform to target tumor sites via active and passive targeting effects, thus avoiding the toxic side effects of nanocarriers and improving the efficacy of chemotherapeutic drug delivery. Methods A sequential stimulus-responsive nanoparticle that targeted the tumor microenvironment and exhibited dual sensitivity to the reduction condition and matrix metalloproteinase-9 (MMP-9) enzyme was fabricated based on a self-assembled polypeptide-paclitaxel conjugate. Results The nanoparticles (48.9 ± 2.1 nm) transformed into rod-like nanostructures (297.1 ± 3.2 nm) in the presence of MMP-9. The rod-like nanostructures were taken up by tumor cells and then sensitive bonds were broken in response to highly expressed GSH in tumor cells to release drugs. This platform showed a tumor inhibition rate of 71.8% in S180-bearing mice and a more effective tumor inhibition rate than Taxol in 4T1-bearing mice. Conclusion This platform facilitates the design of enhanced safe and efficient chemotherapy drug delivery.
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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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2026
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IF 5.4
Weiyong Hong,Haoyu Zhang,Xiuyuan Xia,Mengqian Li,Xugang Ji,Fangyuan Guo,Junbo Cai
PEGylation strategy determines protein corona composition on nanoparticles. • Surface heterogeneity leads to distinct corona-mediated cellular interactions. • Protein corona differentially affects and macrophage uptake tumor targeting. • Surface-dependent corona formation alters in vivo therapeutic efficacy. Active-targeting nanocarriers are promising for precision cancer therapy, but protein corona formation upon blood contact masks targeting ligands and triggers rapid clearance. Here, we investigate how PEG surface architecture (chemical grafting vs. physical coating) modulates protein corona formation and therapeutic outcomes. Using a star-shaped polymer (PET-PCL) functionalized with an MMP-9-targeted and responsive dual-functional peptide, we engineered two types of NPs with similar bulk properties but different surface poly (ethylene glycol) (PEG) configurations: chemical grafting versus physical coating. Quantitative proteomic analyses revealed that serum incubation led to markedly different protein corona profiles. Notably, chemically grafted NPs exhibited significantly lower adsorption of corona, effectively mitigating opsonin-mediated clearance and preserving targeting functionality. Consequently, these corona-coated NPs demonstrated superior cellular internalization in lung cancer cells (A549) and reduced phagocytosis by macrophages (RAW264.7) compared to their physically coated counterparts. Furthermore, in vivo biodistribution studies in A549 tumor-bearing mice confirmed that chemically grafted NPs achieved enhanced tumor accumulation, which corresponded with favorable antitumor activity. Collectively, these findings elucidate the critical role of surface PEG architecture in regulating protein corona formation and demonstrate that tailored surface engineering can harmonize stealth and targeting functionalities. This work provides a rational design strategy for next-generation targeted nanomedicines aimed at overcoming biological barriers in complex physiological environments. Download: Download high-res image (227KB) Download: Download full-size image
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Journal of Materials Chemistry B
·
2015
·Vol. 4
·期 3
·547-556
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IF 4.726
Mengyi Li,Xiaoyan Zhou,Xiaolong Zeng,Changyong Wang,Jiake Xu,Dong Ma,Wei Xue
For effective gene delivery to breast cancer MCF-7 cells, a folate-targeting redox gene carrier was synthesized by Michael addition polymerization between 1-(2-aminoethyl)piperazine and N,N′-cystaminebisacrylamide. Folate was then conjugated through an amidation reaction. The obtained folate-modified hyperbranched poly(amido amine)s (FA-PAAs) degraded in the presence of glutathione and displayed excellent transfection efficiency in vitro. In particular, FA-PAAs showed much higher gene delivery efficiency than PEI-25k in the presence of serum, leading to an obvious decrease in MMP-9 protein expression and the apoptosis of MCF-7 cells. Moreover, FA-PAAs displayed lower cytotoxicity and better blood compatibility than PEI-25k, suggesting a potential application in gene therapy for tumors.
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Asian Journal of Pharmaceutical Sciences
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2026
·
IF 12.6
Chenxiao Chu,Xi Chen,Yaxin Deng,Jie Zhang,Xiaoshuang Bi,Yunfeng Ma,Mingli Wei,Jiansong Zhao,Haibing He,Jingxin Gou,Tian Yin,Xing Tang,Li Yang,Yu Zhang
Corneal neovascularization (CNV), an inflammation-driven pathological process responsible for irreversible vision loss, remains an urgent unmet challenge in ophthalmic medicine. Current interventions—ranging from surgery to topical steroids—fail to prevent recurrence or evade severe side effects like intraocular hypertension and even corneal ulceration. Here, we introduce CL-Peptide-Dex, a transformative contact lens (CL) engineered for matrix metalloproteinase-9 (MMP-9)-responsive dexamethasone (Dex) release, to resolve this decades-long challenge. By grafting dexamethasone on the lens surface via an MMP-9-cleavable peptide linker (GPLGLAGC), CL-Peptide-Dex achieves disease-adaptive drug delivery: rapid release during acute inflammation and sustained release throughout CNV progression. Unlike conventional drug-eluting systems, this surface-grafting strategy eliminates burst release while preserving lens transparency and oxygen permeability. In the rabbit corneal neovascularization model, a single administration of CL-Peptide-Dex could maintain a stable Dex level for 7 days, suppressed VEGF by 77.5%, and reduced neovascular area by 79.5%. Critically, CL-Peptide-Dex avoided intraocular pressure spikes and exhibited good corneal biocompatibility and compliance, enabling safe extended wear. By integrating MMP-9-responsive precision delivery with patient-friendly design, CL-Peptide-Dex represents a significant advance in precision ophthalmology.
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MOLECULAR NEUROBIOLOGY
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2024
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IF 4.6
Wang Ajun,Li Nan,Zhang Nan,Liu Jian,Yang Tao,Li Dongxue,Li Changwen,Li Rui,Jiang Tongcui,Xia Chengyu
The pathogenesis and development of Moyamoya disease are still unclear. This study aimed to investigate the effect of desmoglein-2 (DSG2) on Moyamoya disease and determine the inhibitory effect of DSG2 in vascular remodeling in Moyamoya disease. RNA sequencing, immunohistochemistry (IHC), and western blotting were used to detect the expression of DSG2 in the superficial temporal artery (STA) tissues of Moyamoya disease. The association between DSG2 and endothelial cells’ biological activities was investigated by cell counting kit-8 (CCK-8), migration assay, tube formation assay, flow cytometry with Annexin V-FITC/PI staining, and TUNEL apoptotic cell detection kit. Pathways affected by overexpression or knockdown of DSG2 were identified in endothelial cells. The expression of DSG2 in the STA tissues of Moyamoya disease was lower than that in normal controls. Overexpression of DSG2 inhibits the proliferation and migration but promotes apoptosis in endothelial cells, and low DSG2 levels result in impaired angiogenesis. In addition, there was an interaction between DSG2 and MMP-9, and DSG2 acted through the PI3K signaling in endothelial cells. Our results indicate that DSG2 affects PI3K signaling in vascular endothelial cells, and MMP-9 is involved in DSG2-mediated vascular changes in Moyamoya disease.
研究领域:
神经病学
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血管生物学
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细胞信号
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分子生物学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Xiuru Zhang,Zhuangzhuang Liu,Yuna Li,Jingqin He,Lulu Yang,Yulin Yan,Shanshan Tong,Yeqi Wang,Tao Zhang
Lead (Pb), a persistent heavy metal, has caused widespread environmental contamination due to its extensive industrial use. Among its compounds, lead acetate (PbAc) is particularly hazardous in aqueous form, exhibiting neurotoxic potential. However, its toxic effects on the integrity of the blood-brain barrier (BBB) and the underlying mechanisms remain poorly understood. This study demonstrates that zebrafish embryos exposed to varying concentrations of PbAc exhibit dose-dependent morphological abnormalities, including growth retardation, delayed hatching, and cardiovascular dysfunction, along with pronounced neurobehavioral deficits in both embryonic and adult zebrafish. Live imaging analysis revealed that both acute and chronic exposure to different concentrations of PbAc can induce cerebral hemorrhage and BBB dysfunction. Additionally, PbAc selectively disrupted cerebral angiogenesis without affecting trunk intersegmental vessels and significantly reduced pericyte coverage within both cerebral and trunk vessels. Mechanistically, RNA sequencing and qPCR validation revealed significant upregulation of MMP-9 and MMP-13 in PbAc-exposed embryos. Pharmacological inhibition of MMP-9/13 using polygalacic acid significantly reduced cerebral hemorrhage and restored pericyte coverage, suggesting that these proteases mediate PbAc-induced cerebrovascular damage. Overall, our findings underscore the ecological and public health risks associated with lead contamination and provide a basis for future therapeutic strategies targeting MMPs to mitigate heavy metal toxicity.
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ACS Applied Materials & Interfaces
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2016
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IF 7.145
Yi Zhang,Junkun Duan,Lingguang Cai,Dong Ma,Wei Xue
For cancer gene therapy, a safe and high-efficient gene carrier is a must. To resolve the contradiction between gene transfection efficiency and cytotoxicity, many polymers with complex topological structures have been synthesized, although their synthesis processes and structure control are difficult as well as the high molecular weight also bring high cytotoxicity. We proposed an alternative strategy that uses supramolecular inclusion to construct the aggregate from the small molecules for gene delivery, and to further explore the relationship between the topological assembly structure and their ability to deliver gene. Herein, PEI-1.8k-conjugating β-CD through 6-hydroxyl (PEI-6-CD) and 2-hydroxyl (PEI-2-CD) have been synthesized respectively and then assembled with diferrocene (Fc)-ended polyethylene glycol (PEG-Fc). The obtained aggregates were then used to deliver MMP-9 shRNA plasmid for MCF-7 cancer therapy. It was found that the higher gene transfection efficiency can be obtained by selecting PEI-2-CD as the host and tuning the host/guest molar ratios. With the rational modulation of supramolecular architectures, the aggregate played the functions similar to macromolecules which exhibit higher transfection efficiency than PEI-25k, but show much lower cytotoxicity because of the nature of small/low molecules. In vitro and in vivo assays confirmed that the aggregate could deliver MMP-9 shRNA plasmid effectively into MCF-7 cells and then downregulate MMP-9 expression, which induced the significant MCF-7 cell apoptosis, as well inhibit MCF-7 tumor growth with low toxicity. The supramolecular aggregates maybe become a promising carrier for cancer gene therapy and also provided an alternative strategy for designing new gene carriers.
研究领域:
生物化学
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分子生物学
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药学
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高影响因子
Oncology Letters
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2017
·Vol. 14
·期 5
·5307-5312
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IF 1.39
Binggao Wang,Zhibo Xing,Fengmei Wang,Xinyan Yuan,Yanhui Zhang
In order to improve outcomes after breast cancer treatment, it is essential to understand the mechanisms of action of potential therapeutic agents. The effect of fangchinoline (FAN) on migration and apoptosis of human breast cancer MDA-MB-231 cells and its underlying mechanisms were investigated. MDA-MB-231 cells were treated with different concentrations of FAN, growth inhibition rates were measured by MTT assay and morphological changes of apoptotic cells were observed by Hoechst staining. The wound-healing assay was used to determine of the effect of FAN on the migration of MDA-MB-231 cells. ELISA was used to detect the expression of MMP-2 and -9 in MDA-MB-231 cells treated with different concentrations of FAN and western blot analysis was used to quantify expression of NF-κβ and Iκβ proteins in the same cells. Our results showed that FAN significantly inhibited the growth of MDA-MB-231 cells in concentration-dependent manner and it induced MDA-MB‑231 cell apoptosis. With the high FAN concentrations and long exposure times, the levels of MMP-2 and -9 decreased and the expression of NF-κβ decreased, while the expression of Iκβ protein increased. Based on these results, the antitumor effects of FAN on breast cancer cells can be explained at least partially by inducing apoptosis and inhibiting the migration of MDA-MB-231 cells.
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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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Hanchun Yan,Wei Wang,Xinhua Song,Yaqi Wang,Zhaowen Nie,Honghan Zhang,Hao Duan,Ningyuan Li,Yuqi Feng,Yuhui Zhang,Chao Wang,Zhongchun Liu
Background The underlying mechanisms of major depressive disorder (MDD) remain unclear; however, increasing evidence has linked MDD to blood–brain barrier (BBB) dysfunction. This study aimed to determine whether BBB impairment represents an early pathological change during chronic stress and whether preservation of BBB integrity is associated with attenuation of neuroinflammatory and behavioral abnormalities. Methods We employed a time-course (1, 2, and 4 weeks) chronic unpredictable mild stress (CUMS) model in C57BL/6 J mice. Depressive-like behaviors (SPT, FST, TST, OFT), BBB permeability (Evans blue), tight junction (TJ) protein expression (qPCR, Western Blot), ultrastructure (TEM, IF), peripheral and central inflammatory responses (ELISA, qPCR, IF), and transcytosis-related changes (Western Blot, TEM) were systematically assessed at each time point. In separate intervention experiments, the PDGFRβ inhibitor Imatinib (50 mg/kg/d) or an MMP-9 inhibitor (20 mg/kg/d) was administered throughout the 4-week CUMS procedure. Results Depressive-like behaviors became robustly established by week 4. In contrast, BBB disruption occurred earlier: molecular changes (e.g., Claudin-5 protein loss) were significant at week 1, followed by functional permeability, TJ structural disruption, increased endothelial vesicle density, and inflammatory alterations at week 2. This pathology worsened by week 4. The 4-week Imatinib co-treatment attenuated the development of depressive-like behaviors, alleviated BBB disruption, and reduced neuroinflammatory abnormalities. At the molecular level, CUMS induced a time-dependent upregulation of MMP-9. Imatinib treatment attenuated activation of the PDGFRβ/MMP-9 pathway, whereas MMP-9 inhibition preserved BBB integrity and attenuated central inflammatory abnormalities despite persistently elevated peripheral cytokine levels. Conclusion BBB dysfunction is an early pathological event during chronic stress and is associated with both tight junction disruption and transcytosis-related alterations. Pharmacological preservation of BBB integrity was accompanied by reduced neuroinflammation, consistent with BBB integrity being an important modulator of chronic stress-associated central inflammatory abnormalities. The PDGFRβ/MMP-9 pathway may represent a promising mechanism associated with stress-related BBB injury and a potential therapeutic target.
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Foods
·
2022
·Vol. 11
·期 15
·2360
·
IF 5.561
Haiyan Zheng,Yu Pei,Yuan-Lin He,Yi Liu,Minqi Chen,Pengzhi Hong,Chunxia Zhou,Zhong-Ji Qian
Sulfated polysaccharides from red algae have a variety of biological activities, especially antitumor activities. Matrix metalloproteinase-9 (MMP-9) is a proteolytic metalloenzyme that degrades the central part of the extracellular matrix (ECM) and promotes tumor metastasis. In this research, we have investigated the influence and mechanism of GNP (sulfated polysaccharide fromGelidium crinale) on tumor metastasis and MMP-9 expression of human fibrosarcoma (HT1080) cells. The results inflected that the concentration of GNP below 100 μg/mL has no toxicity to HT1080 cells, but showed excellent activity in inhibiting cells migration and invasion. In addition, GNP effectively inhibits the mRNA of MMP-9 and reduces its expression and activity by regulating nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPK) and mTOR/PI3K/Akt signaling pathways. GNP has great potential as MMP-9 inhibitor and could be developed as a functional food or drug to prevent tumor metastasis.Keywords:sulfated polysaccharides;Gelidium crinale;MMP-9;migration;invasion
研究领域:
药理学
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肿瘤学
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海洋生物学
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高影响因子
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