BIOMATERIALS
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2013
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IF 7.604
Wei-Hai Chen,Xiao-Ding Xu,Hui-Zhen Jia,Qi Lei,Guo-Feng Luo,Si-Xue Cheng,Ren-Xi Zhuo,Xian-Zheng Zhang
A novel strategy to construct a therapeutic system based on functionalized AuNPs which can specifically respond to tumor microenvironment was reported. In the therapeutic system, doxorubicin was conjugated to AuNPs via thiol–Au bond by using a peptide substrate, CPLGLAGG, which can be specifically cleaved by the protease. In vivo study shows that after injection of the functionalized AuNPs to the tumor-bearing mice, the over-expressed protease of MMP-2 in tumor tissue and intracellular GSH can lead to the rapid release of the anti-tumor drug (doxorubicin) from the functionalized AuNPs to inhibit tumor growth and realize fluorescently imaging simultaneously. The functionalized AuNPs with tumor-triggered drug release property can further improve the efficacy and reduce side effects significantly.
研究领域:
纳米医学
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肿瘤学
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生物化学
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DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2022
·
IF 4.319
Na Yin,Hui Yu,Xiaodi Zhang,Xiaodan Lv
Purpose Pancreatic cancer (PCa) is projected to become the second leading cause of cancer-related deaths by 2030. Gemcitabine (GEM) combined with erlotinib (ERL) have been approved by the FDA for locally advanced, unresectable or metastatic pancreatic cancer therapy since 2005. Type-1 matrix metalloproteinase (MT1-MMP) has been recognized as a critical mediator of several steps in PCa progression including activating TGF-β or releasing latent TGF-β from LTBP-1, resulting in increased collagen production and cleavage collagen.Methods In the present research, GEM and ERL co-loaded nanoparticles (GEM/ERL NPs) were prepared. A non-substrate MT1-MMP binding peptide was decorated onto the GEM/ERL NPs surface.Results M-M GEM/ERL NPs exhibited the highest uptake ability (67.65 ± 2.87%), longest half-life period, largest area under the curve, and the best tumor inhibition efficiency (69.81 ± 4.13%). The body weight, blood urine nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of the system were steady when tested in mice model.Conclusion In conclusion, M-M GEM/ERL NPs protected the drugs in the plasma, improved cellular uptake capacity, exhibited the most remarkable tumor cell inhibition ability, and showed the most efficient tumor growth inhibition capacity in vivo. M-M GEM/ERL NPs could be applied as an efficient and safe system for the synergistic combination chemotherapy of PCa.
研究领域:
肿瘤学
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药剂学
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分子生物学
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DOI
PubMed
高影响因子
Science China-Materials
·
2024
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IF 6.8
Duan Yi,Lin Jiangtao,Yue Jiang,Li Yuanyuan,Liao Jinghan,Sun Ying,Wang Quan,Duan Yourong,Li Zhaojun
Atherosclerosis remains a major cause of morbidity and mortality worldwide. Intraplaque neovascularization critically promotes atherosclerotic progression and instability. Vascular endothelial growth factor A (VEGFA) stimulates aberrant microvessel growth in plaques by inducing endothelial cell proliferation and migration. Pigment epithelium-derived factor (PEDF) potently inhibits VEGFA-dependent neovascularization. This study introduces a thermosensitive hydrogel (PFSgel) developed from poloxamer 407 (F127) and sodium alginate (SA) to deliver PEDF locally to atherosclerotic lesions. The PFSgel demonstrated a suitable liquid-solid transition at body temperature (37°C), then forming a stable 3D network structure after SA gelling with the Ca 2+ in the physiological environment which contributed to the character of controlled release. Rheological analysis confirmed its phase transition temperature of 28.7°C and notable self-healing properties, making it ideal for dynamic vascular environments. In vitro experiments showed that PFSgel could suppress VEGFA-induced endothelial cells’ proliferation and migration through modulation of CD31 and MMP-2/MMP-9 signaling. Notably, in vivo degradation test validated the controlled release pattern of PFSgel. In Apoe-deficient atherosclerotic mice, ultrasound-guided PFSgel injection onto the abdominal aorta enabled gradual in situ release of encapsulated PEDF. This effectively reduced plaque burden, neovascularization, and luminal stenosis, even with exogenous VEGFA administration. Histological analyses confirmed reduced lipid deposition, plaque area, and neovascularization within plaques. Overall, this novel in situ -forming PEDF delivery platform enables targeted suppression of pathological neovascularization via CD31 and MMP-2/MMP-9 pathways, representing a promising approach to stabilize high-risk plaques by intervening against VEGFA-dependent neovascularization.
研究领域:
心血管疾病
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药学
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生物医学工程
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DOI
高影响因子
ACS Applied Polymer Materials
·
2026
·Vol. 8
·期 15
·13238-13251
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IF 5.2
Zou Jiaxin,Li Yanan,Kou Zhaojun,Wang Dayang,Lu Linlin,Cong Hailin,Yu Bing,Ma Xuezhen
Although nanodrug delivery systems
have advanced cancer therapy,
limited tumor penetration and inefficient intracellular transport
still restrict their therapeutic efficacy. Herein, we constructed
a matrix metalloproteinase (MMP)-responsive, TAT-containing polymeric
micelle, O@MTPP, for cascade delivery of oxaliplatin in gastric cancer.
O@MTPP integrates an MMP-2/9-cleavable peptide, MTP (GPLGIAG), with
the cell-penetrating and nuclear-localization-associated TAT peptide
(CYGRKKRRQRRR). In the tumor microenvironment, MMP-2/9-mediated cleavage
triggers charge conversion, enhancing tumor-cell internalization and
penetration-associated distribution. After cellular uptake, TAT further
promotes nuclear-associated accumulation of the nanocarrier-associated
payload, supporting improved intracellular delivery of oxaliplatin.
This cascade delivery strategy enhanced tumor accumulation, strengthened
antitumor activity, and induced immunogenic cell death (ICD)-associated
immune responses, including calreticulin exposure, high mobility group
box 1 (HMGB-1) expression, increased tumor necrosis factor-α
(TNF-α), interferon-γ (IFN-γ), and interleukin-12
(IL-12) levels, and decreased interleukin-6 (IL-6). Overall, O@MTPP
provides an enzyme-activated cascade delivery strategy for overcoming
tissue-level and intracellular barriers in oxaliplatin-based gastric
cancer therapy.
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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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高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2025
·
IF 3.4
Lv Saihua,Yang Yuxin,Huang Jianfei
Background Angiogenesis is suggested as pathogenesis of inflammatory bowel disease (IBD). However, how angiogenesis mediates pathogenesis of ulcerative colitis (UC), a common form of IBD, remains elusive. Methods Dextran sulfate sodium salt (DSS)-induced UC mouse models were established. Then, these mice were injected with short hairpin RNA against regenerating family member4 (shREG4), followed by evaluation of weight and disease activity index (DAI). Collected colon tissues underwent hematoxylin and eosin staining and immunohistochemistry to detect morphological changes and microvascular density (MVD). Inflammation cytokines, soluble vascular endothelial growth factor receptor1 (sVEGFR1) and VEGF levels were measured using enzyme-linked immunosorbent (ELISA) assay. Matrix metallopeptidase7 (MMP-7) was measured using western blot. REG4 overexpression plasmid-transfected NCM460 cells experienced quantitative real-time reverse transcription polymerase chain reaction and western blot. Human intestinal microvascular endothelial cells (HIMECs) were co-cultured with NCM460 cells that had been transfected with REG overexpression plasmid and treated with MMP-7 mAb and/or sVEGFR1. MMP-7 or sVEGFR1 levels in both culture medium were tested using ELISA. HIMECs angiogenesis was measured by Angiogenesis kit. Results In vivo, DSS-induced mice exhibited lower weight and higher DAI. Collected mice colon tissues showed enhanced inflammation, morphological changes, MVD, and expressions of VEGF, REG4 and MMP-7, which were all reversed after DSS-induced mice injected with shREG4. In vitro, REG4 overexpression-transfected NCM460 cells and its culture medium presented higher MMP-7 level. After co-culture with REG4 overexpression-transfected NCM460 cells, HIMECs culture medium demonstrated lower level of sVEGFR1 and higher angiogenesis, and the latter was reversed by MMP-7 mAb and/or sVEGFR1 treatment in NCM460 cells. Conclusion REG4 induces angiogenesis in UC by upregulating MMP-7 and downregulating VEGFR1.
研究领域:
胃肠病学
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分子生物学
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血管生成研究
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炎症性肠病
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细胞信号传导
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DOI
PubMed
高影响因子
DENTAL MATERIALS
·
2025
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IF 6.3
Xue Yang,Yadong Chen,Yifan Chen,Jiajia Xu,Honghai Yan,Qiaojie Luo,Wei Yao,Xiaodong Li
Objective To develop a multifunctional strategy based on in-situ copper sulfide (CuS) nanoparticle deposition, aiming to simultaneously mitigate interface-confined water to improve adhesive infiltration, suppress enzymatic degradation, and prevent bacterial colonization. Methods Demineralized dentin matrices (DDM) were sequentially treated with CuSO₄ and Na₂S solutions at three concentrations (0.0015, 0.015, 0.15 mol/L), with conventional wet-bonding as a control. Nanoparticle distribution, matrix dehydration, matrix metalloproteinase (MMP) activity, antibacterial efficacy ( Streptococcus mutans , Staphylococcus aureus and Escherichia coli ), and bonding performance (nanoleakage, microtensile bonding strength) were systematically evaluated. Results Uniform CuS deposition significantly reduced DDM hydration to release the interface-confined water. The 0.015 and 0.15 groups showed enhanced mechanical properties. Moreover, all concentrations of CuS deposition inhibited MMP and showed antibacterial effect. As a result, the 0.015 and 0.15 groups showed improved adhesive infiltration, reduced nanoleakage ( p < 0.05) and increased both immediate and aged microtensile bonding strength ( p < 0.01). Conclusion In-situ CuS nanoparticle deposition synergistically enhances bond durability, through DDM dehydration, MMP inhibition, and antibacterial action. This approach effectively minimizes hybrid layer defects and collectively prolongs bonding longevity. Clinical significance The Cu-assisted bonding technique provides a clinically feasible solution to address multifactorial failure modes in dentin bonding, leveraging nanomaterial synergy for durable adhesive restorations.
研究领域:
口腔材料学
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纳米牙科
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粘接牙科学
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口腔生物学
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 4
·期 3
·547-556
·
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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PubMed
高影响因子
Journal of Pharmaceutical Innovation
·
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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DOI
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Yuan Zhu,Wei-feng Yin,Pei Yu,Chao Zhang,Ming-hui Sun,Ling-yi Kong,Lei Yang
Distal metastases from breast cancer, especially bone metastases, are extremely common in the late stages of the disease and are associated with a poor prognosis. EMT is a biomarker of the early process of bone metastasis, and MMP-9 and MMP-13 are important osteoclastic activators. Previously, we found that meso-Hannokinol (HA) could significantly inhibit EMT and MMP-9 and MMP-13 expressions in breast cancer cells. On this basis, we further explored the role of HA in breast cancer bone metastasis. In vivo, we established a breast cancer bone metastasis model by intracardially injecting breast cancer cells. Intraperitoneal injections of HA significantly reduced breast cancer cell metastasis to the leg bone in mice and osteolytic lesions caused by breast cancer. In vitro, HA inhibited the migration and invasion of breast cancer cells and suppressed the expressions of EMT, MMP-9, MMP-13, and other osteoclastic activators. HA inhibited EMT and MMP-9 by activating the ROS/JNK pathway as demonstrated by siJNK and SP600125 inhibition of JNK phosphorylation and NAC scavenging of ROS accumulation. Moreover, HA promoted bone formation and inhibited bone resorption in vitro. In conclusion, our findings suggest that HA may be an excellent candidate for treating breast cancer bone metastasis.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
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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PubMed
高影响因子
DENTAL MATERIALS
·
2026
·
IF 6.3
Tianjia Huang,Huan Chen,Shuwei Qiao,Boyu Sun,Shuyao Zheng,Haiya Liao,Zuosen Shi,Song Zhu
A multifunctional Myr@ZIF-8 nanoplatform was developed for dentin bonding. • Myr@ZIF-8 exhibited pH-responsive release of myricetin and Zn²⁺. • Myr@ZIF-8 enhanced antibiofilm activity against Streptococcus mutans . • Myr@ZIF-8 stabilized dentin collagen and suppressed MMP activity. • The modified adhesive significantly improved dentin bonding durability. Objectives This study aimed to develop a myricetin-loaded ZIF-8 (Myr@ZIF-8)-modified universal adhesive with antibacterial, collagen-stabilizing, and matrix metalloproteinase (MMP)-inhibitory properties to improve bonding durability. Methods Myr@ZIF-8 nanoparticles were synthesized and characterized. Myr loading efficiency, drug loading, and pH-responsive release were evaluated. Myr@ZIF-8 was incorporated into a universal adhesive at 2.5–10 wt%, and the optimal concentration was selected according to degree of conversion, dentin wettability, and antibiofilm activity. Dentin collagen stability, MMP-mediated gelatinolytic activity, microtensile bond strength (μTBS), interfacial nanoleakage, interfacial mechanical properties, and in vitro cytocompatibility were evaluated. Short-term systemic toxicity was preliminarily assessed by oral gavage of cured adhesive extracts. Molecular docking was performed to investigate potential interactions between myricetin and collagen, MMP-2, and MMP-9. Results Myr@ZIF-8 exhibited a Myr loading efficiency of 50.72%, drug loading of 50.36%, and pH-responsive release. The adhesive containing 5 wt% Myr@ZIF-8 showed the best overall performance, including enhanced antibiofilm activity, improved collagen stability, and reduced MMP-mediated gelatinolytic activity. Incorporation of 5 wt% Myr@ZIF-8 increased immediate μTBS from 22.79 MPa to 32.07 MPa and aged μTBS after 10,000 thermocycles from 13.91 MPa to 27.99 MPa. Molecular docking predicted potential interactions between myricetin and collagen, MMP-2, and MMP-9. The modified adhesive showed acceptable in vitro cytocompatibility, with no obvious short-term systemic toxicity after oral gavage of cured adhesive extracts. Significance These findings demonstrate that Myr@ZIF-8 functions as a multifunctional bioactive nanoplatform and represents a promising strategy for improving bonding durability. Download: Download high-res image (189KB) Download: Download full-size image Schematic diagram of the experimental process.
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高影响因子
危险品化学品经营许可证（带存储）