BIOMACROMOLECULES
·
2024
·
IF 5.5
Jiaqi Song,Liang Shao,Hongwen Yu,Caiting Meng,Guanying Li
Heparan sulfate proteoglycans (HSPGs) play a crucial role in regulating cancer growth and migration by mediating interactions with growth factors. In this study, we developed a self-assembling peptide (S1) containing a sulfate group to simulate the contiguous sulfated regions (S-domains) in heparan sulfate for growth factor binding, aiming to sequester growth factors like VEGF. Spectral and structural studies as well as simulation studies suggested that S1 self-assembled into nanostructures similar to the heparan sulfate chains and effectively bound to VEGF. On cancer cell surfaces, S1 self-assemblies sequestered VEGF, leading to a reduction in VEGF levels in the medium, consequently inhibiting cancer cell growth, invasion, and angiogenesis. This study highlights the potential of self-assembling peptides to emulate extracellular matrix functions, offering insights for future cancer therapeutic strategies.
研究领域:
癌症生物学
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分子生物学
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Lihui Wen,Mengxin Gan,Siying Xiong,Li Dai,Wen Chen,Wen Shi
Diabetic retinopathy (DR) is characterized by pathological angiogenesis, inflammation, and retinal neurodegeneration, leading to vision loss. Current therapies, such as anti-VEGF agents, face challenges of low bioavailability and frequent invasive injections. Connexin43 (Cx43), a gap junction protein, plays a key role in DR progression through its modulation of inflammation and vascular dysfunction. A thermosensitive hydrogel composite was developed to encapsulate siRNA targeting Cx43 (si-Cx43) nanoparticles (NPs) and anti-VEGF (Avastin). The hydrogel was characterized for gelation, injectability, and degradation. In vitro studies evaluated the cytotoxicity, anti-angiogenic effects, and permeability regulation in hyperglycemic retinal cells under hyperglycemic conditions. In vivo therapeutic efficacy was assessed in a diabetic retinopathy rat model. si-Cx43-NPs demonstrated high siRNA encapsulation efficiency and stability, effectively silencing Cx43 expression in retinal endothelial cells. The hydrogel exhibited excellent injectability, temperature-sensitive gelation, and controlled degradation. In vitro, si-Cx43-NPs@Avastin-hydrogel significantly suppressed VEGF expression, reduced angiogenesis, and restored cell permeability under hyperglycemic conditions. In vivo , the hydrogel composite reduced neovascularization, inflammation, and apoptosis, restoring retinal structure and function more effectively than either single-agent treatment alone. Biocompatibility studies confirmed minimal toxicity and favorable degradation. The si-Cx43-NPs@Avastin-hydrogel provides a synergistic and minimally invasive therapeutic strategy for DR by targeting angiogenesis, inflammation, and neuroprotection with sustained drug delivery.
研究领域:
医学
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生物材料学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Xiaojun Cai,Haofang Zhu,Yanmei Zhang,Zhongwei Gu
RNA interference (RNAi) has a great promise in treating various acquired and hereditary diseases. However, it remains highly desirable to develop new delivery system to circumvent complex extra- and intracellular barriers for successful clinical translation. Here, we report on a versatile polymeric vector, bioreducible fluorinated peptide dendrimers (BFPD), for efficient and safe small interfering RNA (siRNA) delivery. In virtue of skillfully integrating all of the unique advantages of reversible cross-linking, fluorination, and peptide dendrimers, this novel vector can surmount almost all extra- and intracellular barriers associated with local siRNA delivery through highly improved physiological stability and serum resistance, significantly increased intratumoral enrichment, cellular internalization, successful facilitation of endosomal escape, and cytosolic siRNA release. BFPD polyplexes, carrying small interfering vascular endothelial growth factor (siVEGF), demonstrated excellent VEGF silencing efficacy (∼65%) and a strong capability for inhibiting HeLa cell proliferation. More importantly, these polyplexes showed superior performance in long-term enrichment in the tumor sites and had a high level of tumor growth inhibition. Furthermore, these polyplexes not only exhibited excellent in vivo antitumor efficacy but also demonstrated superior biocompatibility, compared with LPF2000, both in vivo and in vitro. These findings indicate that BFPD is an efficient and safe siRNA delivery system and has remarkable potential for RNAi-based cancer treatment.
研究领域:
药剂学
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分子生物学
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癌症研究
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纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 23
·期 2
·1-8
·
IF 2.447
Yao Duan,Hejia Li,Xiaohong Dong,Zhaoli Geng,Xinyi Xu,Yi Liu
The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)‑induced apoptosis and differentiation of osteoblasts. Murine MC3T3‑E1 osteoblasts were stimulated with zoledronic acid (ZA) for 7 days. VEGF mRNA and protein expression levels were determined via reverse transcription‑quantitative PCR and western blot analysis, respectively. Cell viability was evaluated using Cell Counting Kit‑8 assay. In addition, the cell apoptotic rate and the expression levels of apoptosis‑related proteins were measured using a TUNEL staining kit and western blot analysis, respectively. To evaluate mineralization, cells were stained with alizarin red, while the secretion levels of alkaline phosphatase (ALP) were measured using the corresponding assay kit. Finally, the expression levels of differentiation‑related proteins and proteins of the Nod‑like receptor family pyrin domain‑containing 3 (NLRP3)/caspase 1/gasdermin D (GSDMD) pyroptosis pathway were measured by western blot analysis. VEGF expression level was notably decreased in ZA‑stimulated MC3T3‑E1 cells. However, the viability of these cells was enhanced following VEGF addition. Furthermore, VEGF attenuated apoptosis, promoted mineralization and increased ALP activity in ZA‑stimulated MC3T3‑E1 cells. The ZA‑mediated decrease in the protein expression of the osteogenic genes osteopontin, osteocalcin and runt‑related transcription factor 2 was restored after MC3T3‑E1 cell treatment with 10 ng/ml VEGF. The present study demonstrated that VEGF could attenuate BP‑induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway.
研究领域:
细胞生物学
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分子生物学
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药理学
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骨质疏松研究
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产品关联
DOI
PubMed
高影响因子
NPG Asia Materials
·
2020
·Vol. 12
·期 1
·1-11
·
IF 8.131
Yuan Zihan,Guo Xiaoshuang,Wei Minyan,Xu Yang,Fang Zhiwei,Feng Yun,Yuan Wei-En
Small-interfering RNA (siRNA) can specifically silence disease gene expression, bringing hope for the effective treatment of gene-related diseases. However, its use in vivo is limited due to the lack of efficient carriers. Therefore, it is necessary to construct carriers with high efficiency, low toxicity and serum stability. As a promising polycation carrier, polyethylenimine (PEI) can be further modified with a fluorine-containing alkyl chain that brings hydrophobic and oleophobic characteristics to its surface. In this study, low molecular weight PEI 1.8 kDa was selected and fluorinated through an anhydride reaction, and the product was named PEIF. In vitro experiments have shown that PEIF/siRNA polyplexes have suitable and stable particle size and potential, compress nucleic acids at a very low w / w ratio, and have the ability to effectively silence specific genes with low cytotoxicity. Compared with the polyplexes prepared using PEI 25 kDa, the PEIF/siRNA polyplexes were more stable in serum, showed a better antiangiogenic ability in in vivo experiments, and had a better tumor inhibition effect. The above results indicate that fluoropolymers based on the fluorine effect have great potential as gene delivery carriers for tumor therapy.
研究领域:
药学
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分子生物学
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癌症研究
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基因治疗
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2023
·
IF 3.2
Jiashuo Liu,Runzhi Xiang,Hongtao Li,Hong Zhu,Jiarui Dang,Zhihui Ran,Huan Deng,Wenjin Xu,Chengjie Xiong,Zhijun Huang,Peihu Xu,Haixing Xu
Here, a novel kind of composite scaffold was fabricated by loading vascular endothelial growth factor (VEGF) and gastrodin liposome (GAS-LP) into electrospun silk fibroin/graphene oxide(SF/GO)nanofibrous and silk fibroin sponge-filled, respectively. Our results demonstrated that VEGF and GAS exhibited different release patterns in vitro which VEGF showed rapid release rate in the first few days while GAS was released slowly and continuously as encapsulated in liposomes. The scaffolds realized the combination of intraneural vascularization drugs and electrical stimulation effectively, leading to enhanced growth of RSC96 cells. Furthermore, the scaffolds could protect RSC96 cells in an inflammatory environment.
研究领域:
生物材料
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组织工程
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神经科学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2019
·Vol. 42
·期 6
·886-891
·
IF 1.54
Yangbiao He,Xujun Lang,Dong Cheng,Zhihao Yang
Previous studies implicated the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in renal fibrosis and found that curcumin could suppress the expression of mTOR. Therefore, the aim of the present study was to investigate the therapeutic effects of curcumin against chronic renal failure (CRF) in a rat model induced by 5/6 nephrectomy through inhibition of mTOR/HIF-1α/VEGF signaling. A total of 70 male Sprague–Dawley rats were divided into seven groups: a sham group, a CRF group, and five treatment groups. Except for the sham rats, all rats underwent 5/6 nephrectomy to induce CRF. The 5/6 nephrectomized rats received treatment with curcumin vehicle, everolimus vehicle, curcumin, everolimus, or the combination of curcumin and everolimus. Everolimus, a specific inhibitor of mTOR, was used as a positive control. At the end of treatment, blood biochemical indexes, proteinuria and the kidney index were detected. Moreover, histological change was examined by hematoxylin and eosin staining, and protein expression levels were detected by Western blotting. The blood biochemical indexes, proteinuria, and kidney index were increased in the CRF group as compared to the sham group, which was accompanied by marked activation of the mTOR/HIF-1α/VEGF pathway. However, curcumin, as well as everolimus, restored or ameliorated these changes. These results indicate that activation of the mTOR/HIF-1α/VEGF signaling pathway plays an important role in the occurrence and development of CRF, and that curcumin has renoprotective effects by blocking activation of this pathway.
研究领域:
药理学
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肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Chanling Yuan,Chunguang Zhu,Qingshuang Lv,Jiahui Shi,Jiacheng Wang,Shiqi Gao,Jiayi Qian,Yanhua Chen,Qiong Wu,Wenjie Mei
Developing drugs for treating glioblastoma has been a significant challenge. Herein, a series of arene ruthenium(II) complexes have been synthesized and investigated as potential candidates to suppress the proliferation and metastasis of glioblastoma. It is found that para-substituent-modified molecules, especially 6, exhibit higher antitumor activity than ortho-substituents. Further studies show that 6 can trigger tumor cell autophagy by regulating the PI3K/AKT/mTOR pathway. Moreover, it is also found that 6 can induce DNA damage in glioblastoma cells through binding and stabilizing VEGF G-quadruplex DNA. Furthermore, it is confirmed that 6 can inhibit the proliferation and metastasis of U87-MG glioblastoma cell in situ xenograft in the zebrafish model. Hence, arene ruthenium(II) complexes can be developed as promising therapeutic agents for glioblastoma treatment in the future.
研究领域:
癌症研究
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药理学
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分子生物学
·
化疗
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2011
·
IF 7.883
Yongjun Liu,Zhijin Chen,Chunxi Liu,Dexin Yu,Zaijun Lu,Na Zhang
Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially in the early stage of tumor. Here, we designed a novel multifunctional polymeric nanoparticle contrast agent (Anti-VEGF PLA-PEG-PLL-Gd NP) simultaneously modified with Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and anti-vascular endothelial growth factor (VEGF) antibody to deliver Gd-DTPA to the tumor area and achieve the early diagnosis of hepatocellular carcinoma (HCC). The Anti-VEGF PLA-PEG-PLL-Gd NPs exhibited high T 1 relaxivity and no obvious cytotoxicity under the experimental concentrations in human hepatocellular carcinoma (HepG2) cells. The results of in vitro cell uptake experiments demonstrated that the uptake process of NPs was both concentration and time depended. Compared with non-targeted NPs, the Anti-VEGF antibody modified NPs showed much higher cell uptake in the HepG2 cells. During in vivo studies , the targeted NPs showed significantly signal intensity enhancement at the tumor site (mouse hepatocarcinoma tumor, H22) compared with non-targeted NPs and Gd-DTPA injection in tumor-bearing mice and the imaging time was significantly prolonged from less than an hour (Gd-DTPA injection group) to 12 h. These results demonstrated that this novel MRI contrast agent Anti-VEGF PLA-PEG-PLL-Gd NPs showed great potential in the early diagnosis of liver tumors.
研究领域:
医学影像学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Rongrong Zhu,Zhaoqi Wang,Peng Liang,Xiaolie He,Xizhen Zhuang,Ruiqi Huang,Mei Wang,Qigang Wang,Yechang Qian,Shilong Wang
Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and is highly expressed in carcinoma, which make it an important target for tumor targeting therapy. Neuroblastoma is the main cause for cancer-related death in children. Like most solid tumors, it is also accompanied with the overexpression of VEGF. Doxorubicin Hydrochloride (DOX), a typical chemotherapeutic agent, exhibits efficient anticancer activities for various cancers. However, DOX, without targeting ability, usually causes severe damage to normal tissues. To overcome the shortages, we designed a novel nano-composite, which is Bevacizumab (Bev) modified SiO 2 @LDH nanoparticles (SiO 2 @LDH-Bev), loading with DOX to achieve targeting ability and curative efficiency. SiO 2 @LDH-DOX and SiO 2 @LDH-Bev-DOX nanoparticles were synthesized and the physicochemical properties were characterized by TEM detection, Zeta potential analysis, FTIR, Raman and XPS analysis. Then in vitro and in vivo anti-neuroblastoma efficiency, targeting ability and mechanisms of anti-carcinoma and anti-angiogenesis of SiO 2 @LDH-Bev-DOX were explored. Our results indicated that we obtained the core-shell structure SiO 2 @LDH-Bev with an average diameter of 253 ± 10 nm and the amount of conjugated Bev was 4.59 ± 0.38 μg/mg SiO 2 @LDH-Bev. SiO 2 @LDH-Bev-DOX could improve the cellular uptake and the targeting effect of DOX to brain and tumor, enhance the anti-neuroblastoma and anti-angiogenesis efficiency both in vitro and in vivo, and alleviate side effects of DOX sharply, especially hepatic injury. In addition, we also demonstrated that angiogenesis inhibitory effect was mediated by DOX and VEGF triggered signal pathways, including PI3K/Akt, Raf/MEK/ERK, and adhesion related pathways. In summary, SiO 2 @LDH-Bev could be a potential VEGF targeting nanocarrier applied in VEGF positive cancer therapy. Statement of Significance This paper explored that a novel core-shell structure nanomaterial SiO 2 @LDH and modified SiO 2 @LDH with Bevacizumab (Bev) to form a new tumor vasculature targeting nanocarrier SiO 2 @LDH-Bev as vector of DOX, which was not reported before. The results indicated that SiO 2 @LDH-Bev could improve the VEGF targeting ability, anti-neuroblastoma and anti-angiogenesis efficiency of DOX. At the same time, SiO 2 @LDH-Bev-DOX could erase the cardiac toxicity and hepatic injury coming from DOX. Tube formation showed SiO 2 @LDH-Bev-DOX had the strongest effect on inhibiting angiogenesis among all the four formulations. SiO 2 @LDH-Bev-DOX could downregulate expression of p-VEGFR and inhibit activation of the Raf/MEK/ERK, p38MAPK, PI3K/Akt and FAK signaling pathways to achieve the goal of anti-angiogenesis. This work provides a novel system for the safe and efficient use of Bev and DOX on Neuroblastoma and explores the mechanism of the function of nano carrier in cancer therapy both in vitro and in vivo.
研究领域:
癌症生物学
·
药学
·
纳米技术
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
European Review for Medical and Pharmacological Sciences
·
2017
·Vol. 21
·期 10
·2316-2328
·
IF 1.778
An G,Zhang WB,Ma DK,Lu B,Wei GJ,Guang Y,Ru CH,Wang YS
Objective To investigate the influence of VEGF/BMP-2 on the proliferation and osteogenic differentiation of rat bone mesenchymal stem cells BMSCs) on PLGA/gelatin composite scaffold. Materials and methods Randomly-oriented nanofibers with different ratios of Poly Lactic-co-Glycolic Acid (PLGA)/gelatin were produced through electrospinning. The mixture of nanofibers and BMSCs was pipetted onto the surface of the scaffolds, and BMSCs/PLGA/gelatin composite was obtained. The surface morphology, chemical structure, hydrophilicity and mechanical property of PLGA/gelatin nanofibers were revealed by scanning electron microscope. In vitro release kinetics of bone morphogenetic protein (BMP-2) and vascular endothelial growth factor (VEGF) were studied using ELISA kits. The cell adhesion, growth and proliferation of BMSCs on scaffolds were observed by scanning electron microscopy. The CCK-8 assay was used to evaluate the effects of VEGF/BMP-2 slow release system on the proliferation of BMSCs on scaffolds. RT-PCR was used to examine the activities of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX-2), and osteocalcin (OCN). Results In each group of cells in the in-vitro experiment, through electron microscope scanning, fiber scaffolds were interconnected three-dimensional reticular structure, BMSCs firmly attached to the fiber surface and internal stent, cells experienced a long spindle, polygon change, and branch-like protrusions on the cell surface were connected. Under the electron microscope, cell proliferation curve and osteogenesis markers (ALP, RUNX-2, OCN) expression in the dual factor group on cell adhesion, proliferation and differentiation were much better than those of blank control group and single factor groups. Conclusions In the successfully constructed gelatin/PLGA nanofiber scaffold, VEGF and BMP-2 can be sequentially released, during which VEGF and BMP-2 can promote the adhesion, proliferation, and differentiation of BMSCs.
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Xuemin Liu,Huihui Wang,Jiajie She,Qiang Zhang,Qingyu Hu,Dongdong Li,Hongliang Wu,Xiaofeng Ye,Ruiying Diao,Xuetao Shi,Liping Wang
Intrauterine adhesions (IUA) are a common gynecologic disease worldwide that can lead to menstrual irregularities, infertility, or repeated pregnancy loss. Biomaterials are used as a physical barrier to separate damaged uterine walls and prevent tissue adhesion. However, most biomaterials cannot prevent or even increase inflammation and fibrosis during implantation, which is crucial for IUA development, limiting their application in treatment. To address this, we developed a hydrophilic hydrogel film with a negative surface potential that can absorb excess positive proinflammatory cytokines to alleviate the inflammatory response and limit endometrial fibre formation. In vitro, the hydrogel film exhibits good biocompatibility and anti-fibroblast adhesion properties, and in vivo, they downregulate the expression level of proinflammatory cytokines and reduce the degree of fibrosis. After loading the hydrogel film with vascular endothelial growth factor (VEGF) and implanting it into the injured rat endometrial cavity, the increased local microvessels and higher endometrial thickness indicated improved endometrial regeneration during IUA treatment. In summary, the hydrogel film capable of efficiently reducing inflammation and decreasing fibrosis provides a promising strategy for treating and preventing IUA difficulties, with broad clinical application potential.
研究领域:
妇科学
·
生物材料科学
·
组织工程
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）