ADVANCED MATERIALS
·
2023
·Vol. 35
·期 42
·2303718
·
IF 29.4
Shuangquan Gou,Gangyang Wang,Yanan Zou,Wenbo Geng,Tingting He,Zizhen Qin,Lingbin Che,Qian Feng,Kaiyong Cai
Developing a drug delivery platform that possesses universal drug loading capacity to meet various requirements of cancer treatment is a challenging yet interesting task. Herein, a self-assembled gelatin/silk fibroin composite (GSC) particle based drug delivery system is developed via microphase separation followed by desolvation process. Thanks to its preassembled microphase stage, this GSC system is suitable for varying types of drugs. The desolvation process fix drugs inside GSC rapidly and densify the GSC structure, thereby achieving efficient drug loading and providing comprehensive protection for loaded drugs. Actually, the size of this brand-new non-pore dependent drug delivery system can be easily adjusted from 100 nm to 20 µm to fit different scenarios. This work selects GSC with 3 µm diameter as the universal inhaled drug delivery platform, which shows an excellent transmucosal penetration and lung retention ability. Additionally, the MMP-9 sensitive degradation property of GSC enhances the targeted efficiency of drugs and reduces side effects. Intestinally, GSC can self-amplify the regulation of innate immunity to reverse the cancerous microenvironment into an antitumor niche, significantly improving the therapeutic effect of drugs. This study of GSC universal drug platform provides a new direction to develop the next-generation of drug delivery system for lung cancer.
研究领域:
药剂学
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生物材料
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 16
·期 2
·1383-1388
·
IF 1.692
Tao Liu,Xidong Wu,Yigang Wang,Xiongjun Hou,Gang Jiang,Ting Wu,Huifen Xie,Minqiang Xie
The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized star‑shaped co‑polymer consisting of β‑cyclodextrin (CD) and a poly(L‑lysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP‑9) small interfering RNA, via CD‑PLLD/DOC/MMP‑9 complexes, into mice implanted with HNE‑1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic co‑polymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CD‑PLLD/DOC/MMP‑9 inhibited HNE‑1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP‑9 was investigated; CD‑PLLD/DOC/MMP‑9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the blood‑brain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE‑1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Xu Lu,Ming Li,Keqiang Bo,Bin Zheng,Xu Hun
A photoelectrochemical (PEC) assay strategy for the detection of matrix metalloproteinase-9 (MMP-9) was fabricated. RuSe 2 /CuO nanohybrids were first prepared by hydrothermal method. As a transition metal element semiconductor, RuSe 2 has excellent optical and electrical properties. By combining the excellent conductivity and adjustable bandgap of CuO, a binary heterojunction nanoflower with high photoelectric response was obtained. The combination of RuSe 2 and CuO reduces the electron hole recombination rate; the RuSe 2 /CuO nanohybrids exhibits a higher photocurrent response. In the MMP-9 PEC strategy determination, the magnetic beads (MB)-peptide-alkaline phosphatase (ALP) recognition probe was formed by modifying C-terminal of the peptide chain with biotin and binding to ALP, and the N-terminal was connected to carboxylated MB. When the target MMP-9 exists, the recognition probe, MB-Peptide-ALP, was recognized by MMP-9 to cut the substrate area and coding area and release ALP, catalyzing the hydrolysis of O-phosphonoxyphenol (OPP) to produce benzene-1,2-diol in situ, the photocurrent response was generated. This strategy provides lower background PEC noise for detecting MMP-9, with the advantage of simplicity and the sensitivity than conventional ELISA. The results showed that the recognition peptide probe PEC method achieved ultra-high sensitivity detection of target MMP-9, with a linear detection range of 1 pg/mL–100 ng/mL and a detection limit of 0.3 pg/mL (S/N = 3). The results of PEC assay strategy in human serum sample give the recoveries rate of 94.3 % to 108.1 % and relative standard deviation of 0.45–5.87 %.
研究领域:
纳米技术
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生物化学
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分析化学
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医学诊断
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Tianjiao Ji,Suping Li,Yinlong Zhang,Jiayan Lang,Yanping Ding,Xiao Zhao,Ruifang Zhao,Yiye Li,Jian Shi,Jihui Hao,Ying Zhao,Guangjun Nie
Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy.
研究领域:
癌症生物学
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药学
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Brain Sciences
·
2022
·Vol. 12
·期 5
·571
·
IF 3.333
Chao Song,Chao Gao,Zhenxin Wang
(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been investigated. (2) Method: Adult male mice received 2.3 mg/kg cisplatin or saline injections for three cycles consisting of five daily injections followed by 5 days of rest. Procyanidin or saline was administered 1 h prior to cisplatin treatment. Cognitive testing, gelatin zymography, and blood–brain-barrier (BBB) penetration tests were performed after treatment cessation. RAW264.7 cells were treated by stimulated supernatant of SHSY5Y cells. In addition, high-mobility group protein B1 (HMGB1) expression and MMP-9 activity were tested. (3) Results: Repeated cisplatin treatment increased BBB penetration, MMP-9 activity, impaired performance in contextual fear conditioning, and novel object recognition tasks. The knockout of MMP-9 rescues cognitive impairment and cisplatin-induced upregulation of HMGB1 in SHSY5Y cells. HMGB1/TLR4/IP3K/AKT signaling contributes to the increased MMP-9 activity in RAW264.7 cells. Procyanidin treatment attenuates MMP-9 activity, BBB damage, and CICI. (4) Conclusions: The results indicated that MMP-9 activation and BBB disruption is involved in CICI. Procyanidin may effectively alleviate the harmful effects of cisplatin.Keywords:cisplatin;chemotherapy;MMP-9;RAW264.7 cells;procyanidin;blood–brain barrier (BBB);chemotherapy-induced cognitive impairment (CICI)
研究领域:
肿瘤学
·
神经科学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Hao Wu,Xuefeng Ding,Yun Chen,Yanfei Cai,Zhaoqi Yang,Jian Jin
Antibody–drug conjugates (ADC) are an inevitable trend in the development of modern “precision medicine”. The goal of this work is to produce enzyme-responsive antibody nanoparticle-loaded medication (FMSN-Dox-H2-AE01) based on the EGFR antibody (AE01) and human serum albumin (HSA) shelled mesoporous silica nanoparticles. HSA and antibodies on the surface of the particlescan not only enhance the biocompatibility of the particle and avoid early drug leakage but also allow selective biodegradation triggered by matrix metalloproteinase-2 (MMP-2), which are overexpressed enzymes in some tumor tissues. The cytotoxicity test confirmed favorable safety and efficacy of the ADC. The mortality rate of cancer cells is about 85–90%. Moreover, the antibody nanoparticle-loaded drug showed distinguishing controlled release efficiency toward cancer cells induced by different levels of MMP-2 and pH. This enzyme-responsive FMSN-Dox-H2-AE01 offers a promising option for cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Xuejiao Zhang,Jiaxin Gu,Congying Zhao,Yaozhong Hu,Bowei Zhang,Jin Wang,Huan Lv,Xuemeng Ji,Shuo Wang
Non-nutritive sweeteners are the most widely used food additives designed to provide sweetness and reduce caloric intake. Studies have confirmed a link between sweeteners and colitis, yet supporting scientific data remain exiguous and controversial. In this study, three common sweeteners (Saccharin sodium, Stevioside, and Sucralose) in acceptable daily intake dosage were added to water in order to determine their effects on dextran sodium sulfate-induced colitis in mice. Our results show that the three sweeteners meliorate colitis to varying degrees─Saccharin exerts the most pronounced effect, followed by Stevioside and Sucralose. Intake of sweeteners alleviates colitis symptoms, alters gut microbiota, reshapes the TH17/Treg balance, protects the intestinal barrier, and reduces inflammation. Most significantly, sweeteners can enhance the abundance of Mucispirillum and Alistipes, which are conducive to colitis recovery, and upregulate the expression of E-cadherin through the miR-15b/RECK/MMP-9 axis to improve intestinal barrier integrity. Moreover, by inhibiting the MMP-9/AKT/NF-κB pathway, inflammation is relieved, as reflected in the restoration of the Th17/Treg balance. Our results link the consumption of sweeteners to the remission of colitis, which provides new scientific evidence for the safe use of sweeteners.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Qiang Chen,Chunjing Guo,Huimin Guo,Yanguo Su,Zhongxin Liu,Min Cao,Daquan Chen
With the improvement of people’s living standards, obesity has become a health threat, but an effective drug treatment for obesity has not been found yet. Here, we suggest the use of celastrol, a pentacyclic triterpenoid from the traditional Chinese medicine Tripterygium wilfordii, which has a powerful antiobesity effect. Increasing studies have discovered that obesity is closely related to inflammation. In addition, MMP-2 enzyme is highly expressed in inflammatory sites. According to the principle of the prodrug, celastrol was used as a hydrophobic group, PVGLIG as a link, and dextran sulfate as a hydrophilic group to form a micelle (DS-PVGLIG-Cel). Celastrol was then loaded for the effective treatment of high-fat-diet (HFD)-induced obesity. MMP-2-sensitive assays confirmed that PVGLIG cleavage by MMP-2 enzymes favors the synchronous release of celastrol. A series of animal experiments tested that the preparation group has a strong weight loss effect. Our results suggest that this will shed light on a strategy for the subsequent effective treatment of HFD obesity.
研究领域:
药学
·
生物医学工程
·
代谢疾病研究
✓ 已验证
DOI
高影响因子
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
·
2020
·
IF 2.802
Qiyu Liu,Zhe Yang,Ning Ma,Weixing Wang,Yangqun Li
This study aimed to investigate the long-term scar hypertrophy in the rabbit transplanted oral mucosa and scrotal skin with changed matrix environment, as well as the scar location expression, quantitative analysis of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and biomechanical changes in the transplanted tissues. The split-thickness skin grafts were collected from the oral mucosas and scrotal skins of 30 male rabbits, and prepared into reelpipes for autologous transplantation into the rabbit back muscular tissues. Samples were collected to carry out elastic tensile mechanical detection and histological observation. The maximum longitudinal tensile displacement of scrotal skin before 8 weeks of transplantation was greater than that after 8 weeks of transplantation (P < 0.05). The expression intensities of MMP-2 and TIMP-2 in the oral mucosa and in scrotal skin at 2 W time point were higher than those at T o time point (P < 0.05). The expression quantities of TIMP-2 in oral mucosa and scrotal skin during 8–24 W were higher than those of MMP-2 (P < 0.05). At 8 W time point, the TIMP-2/MMP-2 ratio in scrotal skin was higher than that in oral mucosa (P < 0.05). MMP-2 and TIMP-2 expression in normal oral mucosa and scrotal skin is weak, but their expression is remarkably up-regulated after 2 weeks of transplantation, revealing that scar formation was related to the high expression of MMP-2 and TIMP-2. At the 8th–24th weeks, the AOD values of TIMP-2 in oral mucosa and scrotal skin are apparently higher than those of MMP-2; moreover, the TIMP-2/MMP-2 ratio in scrotal skin at the 8th week was higher than that in oral mucosa, which can well explain the earlier scar formation in scrotal skin than in oral mucosa, and it also suggests that the different expression levels between TIMP-2 and MMP-2 may account for the important cause of scar formation.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2016
·
IF 6.008
Qianming Lin,Yumeng Yang,Qian Hu,Zhong Guo,Tao Liu,Jiake Xu,Jianping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly( l -lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with α-cyclodextrin (α-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by α-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on α-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system , this supramolecular hydrogel is a promising candidate for long-term gene therapy. Statement of Significance To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between α-cyclodextrin and PEGylated arginine-functionalized poly( l -lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering.
研究领域:
生物材料学
·
基因治疗
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Yiwen You,Zhiyuan Xu,Yun Chen
HER2-positive breast cancer correlates with more aggressive tumor growth, a poorer prognosis and reduced overall survival. Currently, trastuzumab (Herceptin), which is an anti-HER2 antibody, is one of the key drugs. There is evidence indicating that conjugation of trastuzumab with chemotherapy drugs, such as doxorubicin (DOX), for multiple targets could be more effective. However, incomplete penetration into tumors has been noted for those conjugates. Compared to an antibody, peptides may represent an attractive alternative. For HER2, a similar potency has been observed for a 12-amino-acid anti-HER2 peptide mimetic YCDGFYACYMDV-NH2 (AHNP, disulfide-bridged) and full-length trastuzumab. Thus, a peptide, GPLGLAGDDYCDGFYACYMDV-NH2, which consists of AHNP and an MMP-2 cleavable linker GPLGLAGDD, was first designed, followed by conjugation with DOX via a glycine residue at the N-terminus to form a novel DOX-peptide conjugate MAHNP-DOX. Using HER2-positive human breast cancer cells BT474 and SKBR3 as in vitro model systems and nude mice with BT474 xenografts as an in vivo model, this conjugate was comprehensively characterized, and its efficacy was evaluated and compared with that of free DOX. As a result, MAHNP-DOX demonstrated a much lower in vitro IC50, and its in vivo extent of inhibition in mice was more evident. During this process, enzymatic cleavage of MAHNP-DOX is critical for its activation and cellular uptake. In addition, a synergistic response was observed after the combination of DOX and AHNP. This effect was probably due to the involvement of AHNP in the PI3K–AKT signaling pathway, which can be largely activated by DOX and leads to anti-apoptotic signals.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Na Li,Liqun Yang,Chenglin Pan,Phei Er Saw,Meng Ren,Biyun Lan,Junfeng Wu,Xiaoyi Wang,Tingting Zeng,Liyan Zhou,Li-Ming Zhang,Chuan Yang,Li Yan
s The anomalous high expression of matrix metalloproteinase 9 (MMP-9) is one important factor that impedes diabetic wound healing. Therefore, inhibition of MMP-9 expression in a diabetic wound could be a feasible method to promote wound healing. In this study, we studied the possibility of self-therapy using wound dressings that contain bacterial cellulose-hyperbranched cationic polysaccharide (BC-HCP) derivatives that encapsulate siRNA (BC-HCP/siMMP-9) and have controlled release properties. Herein, we used four HCPs (Gly-DMAPA, Gly-D4, Amyp-DMAPA, Amyp-D4) as gene carriers. Our results showed that all HCP derivatives were minimally toxic to cells in vitro , while the cationic properties of HCP could be used as a complexation agent for MMP-9 siRNA (siMMP-9). Upon exposure to bacterial cellulose (BC), the BC slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein levels of MMP-9 in a human immortalized epithelial cell line (HaCAT) and in diabetic rat wounds. Inhibition of MMP-9 in the wounds of diabetic rats resulted in a significant enhancement of wound healing, suggesting that the BC-HCP/siMMP-9 composite dressing could be used as a safe and effective dressing to promote wound healing in diabetic rats. Statement of significance In this work, we evaluated the possibility of using bacterial cellulose-hyperbranched cationic polysaccharide derivatives (BC-HCP) as a self-therapeutic wound dressing with siRNA encapsulated and controlled release properties. Our results showed that the BC-HCP/siMMP-9 composite dressing slowly released HCP/siMMP-9. The released siMMP-9 effectively reduced the gene expression and protein level of MMP-9 in human immortalized epithelial cell line and in the wound of diabetic rats. The BC-HCP/siMMP-9 composite dressing promoted diabetic wound healing by the unique nanostructure of BC and by releasing siMMP-9 for specific MMP-9 inhibition. Therefore, it could be used as a safe and effective dressing to promote wound healing in diabetic rats. This is the first evidence on the study of using BC as a dressing composite by encapsulating HCP/siRNA complexes for efficient RNAi gene silencing for better wound healing in diabetic rats.
研究领域:
生物医学工程
·
药剂学
·
伤口愈合
·
糖尿病
·
基因治疗
✓ 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）