POWDER TECHNOLOGY
·
2018
·
IF 3.23
Chao Qin,Xin Yang,Yubing Wu,Yaqi Lv,Li Zhang,Xiaofei Xin,Lei Yang,Wei He,Xiaopeng Han,Lifang Yin,Chunyong Wu
ABSTRACT A matrix metalloproteinases (MMPs) triggered multifunctional micellar system loading traditional chemotherapeutic agent paclitaxel (PTX) and marimastat (MATT), an inhibition of matrix metalloproteinases, was established to prevent tumor growth and metastasis. The micelles were self-assembled by the conjugate synthesized with an MMPs sensitive peptide as the bridge between PTX and poly(ethylene glycol) (PEG). 4T1 cell line derived from a murine breast tumor was selected as the cell model due to its high metastasis. The cytotoxicity assay and cell apoptosis analysis revealed that the sensitive micelles increased the toxicity and cell apoptosis compared with the insensitive micelles. In addition, this system also exhibited high penetration ability in tumor spheroids and significant invasion inhibition with the method of Transwell invasion assay. In the BALB/c mice bearing 4T1 tumors, this system inhibited the growth of the metastatic tumor and prevented the incidence of lung metastasis with low systemic toxicity. And the expression of MMP-2 and MMP-9, which are important in the process of tumor metastasis, was down-regulated. Generally, the data obtained from the in vitro and in vivo studies confirmed that the codelivery of PTX and MATT by the MMPs sensitive micelles achieved not only significant antitumor effect but also obvious inhibition effect of tumor metastasis, which are the leading cause of cancer deaths. This functional particle system may provide a promising strategy for metastatic breast cancer therapy.
研究领域:
肿瘤学
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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
高影响因子
Frontiers of Materials Science
·
2023
·Vol. 17
·期 4
·1-12
·
IF 2.7
Hou Changxin,Xing Huike,Yuan Xubo
Monoclonal antibodies have been used in many diseases, but how to improve their delivery efficiency is still a key issue. As the modification of zwitterionic polymers can maintain the stability and biological activity of monoclonal antibodies, in this study, zwitterionic monomers, sulfobetaine methacrylate (SBMA), and 3-[[2-(methacryloyloxy) ethyl] dimethylammonio] propionate (CBMA) were used to prepare monoclonal antibody-loaded zwitterionic nanoparticles with the aid of the crosslinker of MMP-2 enzyme-responsive peptide which was a rapid synthesis process under mild conditions. The results from dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) indicated that a series of zwitterionic nanoparticles had been successfully prepared by the in situ free radical polymerization using the MMP-2 enzyme-responsive peptide as the cross-linking agent. These nanoparticles were spherical with the sizes of (18.7±1.9) nm (SBMA nanoparticle) and (18.2±2.1) nm (CBMA nanoparticle), and the surface contained zwitterionic polymers. It was revealed that they had no cytotoxicity, could be released in tumor microenvironment by enzyme to inhibit the growth of tumor cells, and was able to effectively penetrate endothelial cells (> 2%) by transwell. Therefore, the development of this strategy has a great prospect for the delivery of monoclonal antibodies.
研究领域:
药学
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纳米技术
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生物医学工程
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癌症研究
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DOI
高影响因子
EXPERIMENTAL LUNG RESEARCH
·
2023
·
IF 1.7
Ting Yang,Chang Xu,Niu Ding,Shujuan Luo,Bichen Wu,Shijie Jin,Yanping Chen
Background To investigate the protective effect of p14ARF in a nitric acid (NA) aerosol inhalation-induced bronchiolitis obliterans (BO) mouse model and its potential regulatory mechanism.Methods A BO mouse model was established by NA aerosol inhalation. The expressions of p14ARF, phosphatidylinositol-3-kinase (PI3K), and protein kinase B (AKT) were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot (WB). Hematoxylin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining observed pulmonary histological changes. TdT-mediated dUTP nick end labeling (TUNEL) staining detected pulmonary cell apoptosis, and enzyme-linked immunosorbent assay (ELISA) measured matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukon-6 (IL-6), and transforminh growth factor-β (TGF-β) levels in lung tissue and bronchoalveolar lavage fluid (BALF).Results The expressions of p14ARF, PI3K, and AKT showed a time gradient change, with a decrease trend (*P < 0.05 and **P < 0.01). Severe inflammatory infiltration and tracheal fibrosis were found in lung tissue in the modeling group (BO group) compared with the control group (Con group). The pH, PaO2, and PaO2/FiO2 values significantly reduced, while the PaCO2 value and the number of TUNEL-positive cells increased in BO group (P < 0.05). In addition, MMP-2, MMP-9, IL-6, and TGF-β levels remarkably increased, with an increase in the number of white blood cells, neutrophils, and lymphocytes in BO group (P < 0.05). Furthermore, p14ARF up-regulation reversed the trend of the aforementioned indexes in BO mice.Conclusions p14ARF ameliorated the inflammatory response and airway remodeling in a BO mouse model via the PI3K/AKT pathway.
研究领域:
呼吸医学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Jianwei Bao,Minxing Hu,Yuanmei Zhang,Qianqian Zhang,Feiyan Zhu,Qianli Zou,Jihui Tang
Micelles have been extensively investigated as drug delivery systems for loading of antitumor drugs with the advantages of good dispersibility, controllable size distribution, and high loading capacity. However, phagocytic clearance by the mononuclear phagocyte system remains a major impediment that inhibits blood circulation and thus tumor accumulation of micelles. Inspired by the antiphagocytic properties of β 2 -microglobulin (β 2 M), here we developed a β 2 M-derived peptide for the surface functionalization of micelles. A β 2 M-derived sequence was integrated with a matrix metalloproteinase-2 (MMP-2) cleavable sequence and then modified on the surface of poly(ethylene glycol)-b-poly(caprolactone) (PEG-PCL) micelles, endowing the micelles with both antiphagocytic and MMP-2-responsive properties. Compared to pristine PEG-PCL micelles, micelles modified with the dual-functional peptide exhibited higher inhibition of phagocytosis by macrophages in the absence of MMP-2, and enhanced internalization by tumor-associated macrophages in the presence of MMP-2, leading to enhanced tumor accumulation of the loaded photosensitizer, thus enabling antitumor therapy. These results demonstrated that antiphagocytic peptides derived from endogenous proteins are promising for functionalization of micelles in smart drug delivery.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 45
·2004851
·
IF 16.836
Xilin Li,Funeng Xu,Yang He,Yan Li,Jianwen Hou,Guang Yang,Shaobing Zhou
The high incidence of postoperative recurrence and metastasis has a serious effect on survival in breast cancer patients. Moreover, it is still a great challenge to prevent the postoperative recurrence and metastasis through traditional implantable devices due to their inability to control multiple drug release. Herein, an implantable hierarchical structured ultrafine fiber device with a time-programmed drug release function for the local postoperative adjuvant chemotherapy of breast cancer is developed. The structure is obtained through a co-axial electrospinning technology by the formation of the periodically arranged chambers inside a fiber matrix. The Doxorubicin hydrochloride in these chambers is released rapidly, killing the residual tumor cells to prevent tumor recurrence; while the matrix metalloproteinases-2 (MMP-2) inhibitor disulfiram in the fiber matrix is released in a sustained manner, inhibiting tumor invasion to prevent its metastasis. The fiber device implanted in tumor-bearing mice after a surgical tumor reduction displays excellent therapeutic efficacy by preventing both recurrence and metastasis. The mechanism investigation of tumor invasion through the type-II collagen immunofluorescence analysis reveals that the decrease of the activity of MMP-2 plays a key role in this process.
研究领域:
肿瘤学
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生物医学工程
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药学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Arabian Journal of Chemistry
·
2024
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IF 5.3
Yuanquan Ran,Lanlan Yang,Xiaoyan Jia,Huan Zhao,Qiong Hu,Bing Yang,Dongxin Tang,Minyi Tian
Background Akebia trifoliata is a widely distributed medicine and food homology plant. Its fruit is used to treat tumors and the seed’s weight proportion exceeds 50%. However, the anti-tumor effect of A. trifoliata seed remains poorly studied. Methods UHPLC-Q-Orbitrap-MS was used to identify the chemical components of A. trifoliata seed water extract (WE) and ethanolic extract (EE), and their cytotoxicity was evaluated using MTT assay. Further, colony formation and cell cycle assays examined the anti-proliferative effect of A. trifoliata seed EE. Next, morphology observation, AO/EB staining, Hoechst 33,258 staining, Annexin V-PE/7-AAD staining, and JC-1 assays were employed to detect apoptosis. The influence of A. trifoliata seed EE on A549 cell metastasis was assessed by wound healing and transwell invasion tests. In addition, western blotting and network pharmacology were applied to further analyze its anticancer mechanism. Results Eighty-two components were characterized from the A. trifoliata seed WE and EE. For anticancer activity, A. trifoliata seed EE exhibited high cytotoxicity against cancer cells A549 (IC 50 : 52.38 ± 1.04 μg/mL) and NCI-H1299 (IC 50 : 70.29 ± 0.58 μg/mL) and revealed low cytotoxicity against non-cancer cells MRC-5 (IC 50 : 101.28 ± 2.84 μg/mL) and L929 (IC 50 : 113.44 ± 0.55 μg/mL). A. trifoliata seed EE suppressed A549 cell proliferation by inducing S-phase arrest via down-regulation of CDK2 and p21 as well as up-regulation of cyclin E1 and E2. It increased the Bax/Bcl-2 ratio, reduced mitochondrial membrane potential (ΔΨm), activated caspase-9 and caspase-3, cleaved PARP, and triggered apoptosis through the mitochondrial pathway. Besides, it repressed migratory and invasive ability by reducing MMP-2, MMP-9, and N-cadherin levels. Conclusion A. trifoliata seed EE exhibits outstanding anticancer properties and has the exploitation potential as an anticancer drug in the pharmaceutical industry.
研究领域:
药理学
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肿瘤学
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植物科学
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细胞生物学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2021
·Vol. 47
·期 5
·1-11
·
IF 4.101
Yunsheng Liu,Xiangping Xu,Han Tang,Yuchen Pan,Bing Hu,Guodong Huang
There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.
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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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2018
·Vol. 15
·期 4
·e1800024
·
IF 1.617
Qi-Zhe Gong,Di Xiao,Feng Feng,Xiao-Dong Wen,Wei Qu
ent -Sauchinone, a lignan isolated from Saururus chinensis ( Lour .) Baill ., was reported that it could modulate the expression of signal transducer and activator of transcription 3 (STAT3). Since STAT3 plays a key role in invasion, migration, and metastasis of cancer, we investigated whether ent -sauchinone could exert promising inhibitory effects on the invasion and migration of the metastatic human liver cancer cell line SMMC-7721 in the present study. ent -Sauchinone was extracted from dried herbs of Saururus chinensis ( Lour .) Baill . Human liver cancer cell lines SMMC-7721 and HCCLM3 were used to test the effect of ent -sauchinone on cell viability. The IC 50 values and time-dependent effect of ent -sauchinone were determined by MTT assay. Cell migration and invasion of SMMC-7721 were evaluated by the wound healing test and transwell assay respectively, the known anti-metastasis agent curcumin was used as a positive control. Western blotting assay was used to investigate relevant molecular mechanisms of cell invasion and migration. Though ent -sauchinone didn't show high cytotoxicity, the wound healing assay and transwell migration assay revealed a profound impairment in the metastatic potential of SMMC-7721 cells due to down-regulation of N-cadherin, MMP-2, and MMP-9 proteins induced by inhibiting the phosphorylation of STAT3. These findings suggest that ent -sauchinone could be used as a promising agent to treat cancer metastasis.
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
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Can Wang,Ruina Cui,Congying Niu,Xiali Zhong,Qicheng Zhu,Di Ji,Xianjie Li,Hongxia Zhang,Chunqiao Liu,Lina Zhou,Yanli Li,Guowang Xu,Yanhong Wei
The residue of polychlorinated biphenyls (PCBs) exists throughout the environment and humans are subject to long-term exposure. As such, the potential environmental and health risk caused by low-dose exposure to PCBs has attracted much attention. 3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB126), the highest toxicity compound among dioxin-like-PCBs, has been widely used and mass-produced. Cardiotoxicity is PCB126's crucial adverse effect. Maintaining proper metabolism underlies heart health, whereas the impact of PCB126 exposure on cardiac metabolic patterns has yet to be elucidated. In this study, we administered 0.5 and 50 μg/kg bw of PCB126 to adult male mice weekly by gavage for eight weeks. Pathological results showed that low-dose PCB126 exposure induced heart injury. Metabolomic analysis of the heart tissue exposed to low-dose PCB126 identified 59 differential metabolites that were involved in lipid metabolism , amino acid metabolism, and the tricarboxylic acid (TCA) cycle. Typical metabolomic characteristic of cardiac hypertrophy was reflected by accumulation of fatty acids (e.g. palmitic, palmitoleic, and linoleic acid), and disturbance of carbohydrates including D-glucose and intermediates in TCA cycle (fumaric, succinic, and citric acid). Low-dose PCB126 exposure increased glycine and threonine, the amino acids necessary for the productions of collagen and elastin . Besides, PCB126-exposed mice exhibited upregulation of collagen synthesis enzymes and extracellular matrix proteins, indicative of cardiac fibrosis. Moreover, the expression of genes related to TGFβ/PPARγ/MMP-2 signaling pathway was perturbed in the PCB126-treated hearts. Together, our results reveal that low-dose PCB126 exposure disrupts cardiac metabolism correlated with hypertrophy and fibrosis. This study sheds light on the underlying mechanism of PCBs' cardiotoxicity and identifies potential sensitive biomarkers for environmental monitoring.
研究领域:
毒理学
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心脏病学
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环境健康
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Materials
·
2024
·
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
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2016
·Vol. 26
·期 47
·8735-8745
·
IF 11.382
Yuming Yang,Caixia Yue,Yu Han,Wei Zhang,Aina He,Chunlei Zhang,Ting Yin,Qian Zhang,Jingjing Zhang,Yao Yang,Jian Ni,Jielin Sun,Daxiang Cui
Cancer therapeutic drugs face various transportation barriers in transit to the tumor site, making the delivery of effective drug concentrations problematic. Moreover, these drugs are very difficult to use due to their adverse off-target effects. Thus, it is very essential to develop a drug delivery system that can deliver drugs to achieve effective local concentrations without side effects on healthy tissues. Herein, the authors report a self-assembled nanodrug system in which hydrophobic antitumor drugs are packaged into nanoparticles to improve water solubility, tumor targeting ability, blood retention time, and chemotherapeutic effect. The nanodrugs are degraded into smaller ones when exposed to the tumor microenvironment, extravasated from leaky regions of the tumor vasculature, and displayed matrix metalloproteinase-2 (MMP-2)-induced degradation and antitumor property. To construct this unique system, an amphiphilic multifunctional molecule (Pep-Cy5) is synthesized by attaching a MMP-2-cleavable peptide to a hydrophobic near-infrared dye, Cy5. Two hydrophobic anticancer drugs are conjugated to Pep-Cy5 through hydrophobic interactions to form the self-assembled nanodrug system. The MMP-2-induced degradation and hydrophobic antitumor drug interchangeability features of this nanosystem enable the hydrophobic antitumor drugs to exhibit longer blood-retention times, improved intratumoral accumulation, fewer side effects, and higher anticancer efficacies compared with free drugs.
研究领域:
癌症治疗
·
纳米医学
·
药学科学
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
·
2019
·
IF 4.745
Ling Yin,Hao Sun,Meng Zhao,Anna Wang,Shanshan Qiu,Yinjia Gao,Jianan Ding,Shun-Jun Ji,Haibin Shi,Mingyuan Gao
Lymphatic metastasis is an important prognostic indicator for cancer progression. It is therefore considerably meaningful to develop molecularly targeted imaging probes for noninvasive and accurate identification of metastatic lymph nodes (MLNs) at early stages of tumor metastasis. Herein, we report a novel matrix metalloproteinase-2 (MMP-2)-activatable probe constructed with a near-infrared dye (Cy5), a quencher (QSY21), and a tumor-targeting peptide cRGD covalently linked through a radionuclide (125I)-labeled peptide substrate for accurate detection of MLNs. Upon cleavage with activated MMP-2, the above probe emitted MMP-2 concentration-dependent near-infrared fluorescence, which allows sensitive and specific visualization of MLNs via both optical and single-photon emission computed tomography imaging techniques. We thus envision that this probe would serve as a useful tool for studying tumor-induced lymphangiogenesis.
研究领域:
癌症生物学
·
分子影像学
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生物医学工程
✓ 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）