JOURNAL OF LUMINESCENCE
·
2016
·
IF 2.693
Lili Pang,Hongjing Cui,Yu Liu,Wenying Zhong
The dual-function anti-VEGF antibody conjugated CdHgTe quantum dots with good targeting property was successfully prepared. In this system, anti-VEGF antibody is not only a target agent but also a therapeutic drug. The anti-VEGF antibody conjugated near-infrared quantum dots can achieve the purposes of detection and treatment at the same time. As-prepared dual-function fluorescent probe in this work has been successfully applied for in vivo and in vitro imaging, which is promising in rapid tumor detection.
研究领域:
生物医学工程
·
分子影像学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Fanyong Yan,Xiaodong Sun,Tengchuang Ma,Yan Zhang,Yingxia Jiang,Ruijie Wang,Cong Ma,Junfu Wei,Li Chen,Yali Cui
Carbon dots (CDs) as a fluorescent nanomaterial plays an important role in bioimaging and light-emitting devices, and its multifunctionalization will be a promising evolution. Here, by a freely rotatable single bond to connect materials with complementary functions together, a dual-function aggregation-induced emission (AIE) CDs ( V-CDs ) is obtained to visually monitor the dead of cancerous cells and inhibit the production of vascular endothelial growth factor (VEGF). The fluorescence of V-CDs will change between blue and green as the changes of environment viscosity based on the restriction of intramolecular rotation (RIR) effect. For another, the VEGF content decreased by about 3 times compared with the blank group after V-CDs was introduced. The co-administration group shows the best anti-cancer effect among the rest of control groups after Taxol was involved, and the same result are achieved in vitro and vivo . The performances of V-CDs make it possible to realize the potential of visualizing anti-cancer process.
研究领域:
纳米技术
·
生物成像
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
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
·
分子生物学
✓ 已验证
产品关联
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
JOURNAL OF NANOPARTICLE RESEARCH
·
2015
·Vol. 17
·期 5
·1-14
·
IF 2.184
Zhao Qian,Li Nannan,Shu Chang,Li Ruixin,Ma Xiaona,Li Xuequan,Wang Ran,Zhong Wenying
Abstract A novel antitumor drug delivery system, docetaxel (DTX)-loaded oxidized single-wall carbon nanohorns (oxSWNHs) with anti-VEGF monoclonal antibody (mAb) as a target agent was constructed. DTX was absorbed onto the oxSWNHs via the physical adsorption or π–π interaction. DSPE–PEG–COOH was non-covalently wrapped to the hydrophobic surface of oxSWNHs to improve its water solubility and biocompatibility. The mAb was bonded to the PEG through amide bond. The DTX@oxSWNHs-PEG-mAb (DDS) exhibited suitable particle size (191.2 ± 2.1 nm), good particle size distribution (PDI: 0.196), and negative zeta potential (−24.3 ± 0.85 mV). These features enhanced permeability and retention (EPR) effect and reduced the drug molecule uptake by the reticuloendothelial system. The in vitro drug release followed non-Fickian diffusion ( n = 0.6857, R = 0.9924) with the cumulative release of DTX 59 ± 1.35 % at 72 h. Compared with free DTX, the DDS enhanced the cytotoxicity in MCF-7 cell lines in vitro efficiently (IC 50 : 2.96 ± 0.6 μg/ml), and provided higher antitumor efficacy (TGI: 69.88 %) in vivo. The histological analysis indicated that the DDS had no significant side effect. Therefore, the new DDS is promising to attain higher pharmaceutical efficacy and lower side effects than free DTX for cancer therapy. The research demonstrated that DTX@oxSWNHs-PEG-mAb might have promising biomedical applications for future cancer therapy. Graphical Abstract
研究领域:
纳米医学
·
肿瘤学
·
药剂学
✓ 已验证
DOI
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
·
分子生物学
·
癌症研究
·
基因治疗
✓ 已验证
产品关联
DOI
高影响因子
MICROVASCULAR RESEARCH
·
2021
·
IF 3.514
Yi Wang,Yang Yao,Rong Li,Binghui Wu,Huiqin Lu,Jing Cheng,Zhe Liu,Junhui Du
Introduction Choroidal neovascularization (CNV) is the main pathological change of wet age-related macular degeneration. Anti-VEGF drugs are the most commonly used treatment for CNV. The biggest drawback of anti-VEGF drugs is the recurrence of CNV, which requires repeated therapy several times. Autophagy activation may be involved in reducing the therapeutic effect of anti-VEGF drugs. So, this study aims to elucidate the effect and mechanism of anti-VEGF drugs on endothelial autophagy and neovascularization in vitro. Methods RF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O 2 , 5% CO 2 , 94% N 2 ), anti-VEGF group (group1: Ranibizumab 100 μg/ml; group2: Aflibercept , 400 μg/ml; group3: Conbercept , 100 μg/ml). Autophagy-related proteins were examined by Western blot . RFP-GFP-LC3 was used to detect autophagy and autophagic flow. Subsequently, we used autophagy inhibitors (3-MA or CQ) to inhibit Conbercept induced autophagy and to observe its effect on angiogenesis in vitro. Proliferation, migration, and tube formation of endothelial cells can be used to study neovascularization in vitro. In this research, the CCK-8 assay was used to detect cell proliferation . Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Flow cytometry and Tunel were used to detect cell apoptosis . Finally, the mechanism of Conbercept activated autophagy was studied. Western blot was used to detect the expression of p53 and DRAM (damage-regulated autophagy modulator), upstream activators of autophagy. Results The protein levels of Beclin-1 and LC3-2/1 in Ranibizumab and Conbercept groups were significantly higher than in the hypoxia group( P < 0.05). While the expression of P62 was decreased ( P < 0.05). The autophagic flux was showed the same results. However, Aflibercept showed the opposite effect on autophagy. Compared with the Conbercept group, autophagy inhibitor 3-MA or CQ can further inhibit cell proliferation and promotes cell apoptosis ( P < 0.05). Conbercept significantly inhibited cell migration compared with the hypoxia group (633.08 ± 72.52 vs. 546.33 ± 24.61), while the autophagy inhibitor group (3-MA or CQ) had a more obvious inhibition effect (309.75 ± 86.36 and 263.33 ± 68.67) ( P < 0.05). For tube formation, the number of tube formation was decreased significantly in the Conbercept group (32.00 ± 2.00) compared to the hypoxia group (39.00 ± 1.53) and even further reduced in 3-MA or CQ group (24.00 ± 3.61, 20.00 ± 2.65). The length of master segments in the hypoxia group was 15,668.00 ± 894.11. It was decreased in Conbercept (13,885.34 ± 730.03). In 3-MA or CQ group, the length of master segments dropped further (11,997.00 ± 433.66, 10,617.67 ± 543.21). Compare with the hypoxia group, the expression P53 and DRAM were increased in the Conbercept group ( P < 0.05). Autophagy-related proteins LC-3, Beclin-1, and DRAM were inhibited by P53 inhibitor Pifithrin-α (PFTα) ( P < 0.05). Conclusion Ranibizumab and Conbercept can trigger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of Conbercept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of the p53/DRAM pathway.
研究领域:
眼科学
·
细胞生物学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
An Shao,Lulu Jin,Yanni Ge,Ziqiang Ye,Mingyu Xu,Yifan Zhou,Yingyu Li,Linyan Wang,Pinglong Xu,Kai Jin,Zhengwei Mao,Juan Ye
Retinal neovascularization (RNV), a typical pathological manifestation involved in most neovascular diseases, causes retinal detachment, vision loss, and ultimately irreversible blindness. Repeated intravitreal injections of anti-VEGF drugs were developed against RNV, with limitations of incomplete responses and adverse effects. Therefore, a new treatment with a better curative effect and more prolonged dosage is demanding. Here, we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176, appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization. C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection. The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated “eat me” signal, which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically. A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models. In conclusion, these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.
研究领域:
眼科学
·
纳米技术
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2022
·
IF 13.364
J. Li,Q. Tian,H. Sun,Y. Zhang,X. Yang,P. Kaur,R. Wang,Y. Fang,H. Yan,X. Du,L. Ye,G. Zhai
As a common multifactor fundus lesion, choroidal neovascularization (CNV) has become the leading cause of severe vision loss in the elderly. The mainstay treatment is an invasive intravitreal injection of anti-VEGF drug, which leads to a short half-life, incomplete response, and severe ocular complications. In this work, we have developed a novel, liposome-loaded, injectable hydrogel (cSA@Lip-HAC) by a minimally invasive sub-tenon's injection for CNV treatment. First, the multitarget angiogenic inhibitor (sunitinib) and hypoxia-inducible factor inhibitor (acriflavine) were co-loaded in the liposome, which was then loaded in the injectable hydrogel. The in vitro results showed that the cSA@Lip-HAC group had a strong anti-angiogenesis effect. After sub-tenon's injection, the hydrogel endowed the drug-loaded liposome with a longer retention time in the target area. In the CNV model, cSA@Lip-HAC showed a significant anti-CNV effect, which was superior to that of intravitreal injection of a commercial product (Conbercept). Exploration of the molecular mechanism revealed that cSA@Lip-HAC did not only inhibit CNV through the AKT/mTOR/HIF-1α/VEGF signal pathways but also inhibit VEGF R1 and VEGF R2. In conclusion, this novel drug delivery system, combining the merits of the liposome and hydrogel, showed an enhanced anti-CNV effect, thus providing a new and minimally invasive alternative for the treatment of neovascular ocular diseases.
研究领域:
眼科学
·
药学
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Siyue Chen,Yuming Liu,Yutian Zhang,Xu Guo,Tinghui Bai,Kai He,Yanfang Zhu,Yi Lei,Mei Du,Xiaohong Wang,Qiang Liu,Hua Yan
Background and Purpose Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. Experimental Approach Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1 -knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. Key Results BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. Conclusion and Implications BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis. Graphical
研究领域:
眼科学
·
免疫学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Jiahua Li,Yafeng Hao,Huizhuo Pan,Yingying Zhang,Guohui Cheng,Baona Liu,Jin Chang,Hanjie Wang
Vascular endothelial growth factor (VEGF) is the key regulator in neovascular lesions. The anti-VEGF injection is a major way to relieve retinal neovascularization and treat these diseases. However, current anti-VEGF therapeutics show significant drawbacks. The reason is the inability to effectively control its therapeutic effect. Therefore, how to controllably inhibit the VEGF target is a key point for preventing angiogenesis. Here, a CRISPR-dCas9 optogenetic nanosystem was designed for the precise regulation of pathologic neovascularization. This system is composed of a light-controlled regulatory component and transcription inhibition component. They work together to controllably and effectively inhibit the target gene’s VEGF. The opto-CRISPR nanosystem achieved precise regulation according to individual differences, whereby the expression and interaction of gene was activated by light. The following representative model laser-induced choroid neovascularization and oxygen-induced retinopathy were taken as examples to verify the effect of this nanosystem. The results showed that the opto-CRISPR nanosystem was more efficacious in the light control group (NV area effectively reduced by 41.54%) than in the dark control group without light treatment. This strategy for the CRISPR-optogenetic gene nanosystem led to the development of approaches for treating severe eye diseases. Besides, any target gene of interest can be designed by merely replacing the guide RNA sequences in this system, which provided a method for light-controlled gene transcriptional repression.
研究领域:
分子生物学
·
光遗传学
·
纳米技术
·
眼科学
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
BIOMATERIALS
·
2025
·
IF 12.9
Mengtian He,Dayang Xie,Qiannan Cao,Mingxia Jiang,Hongqian Liu,Yingli Yao,Wenming Zheng,Huilin Yuan,Pijun Su,Siting Zhang,Yuxuan He,Shuting Zeng,Yaqing Zeng,Huapan Fang,Hong Wu,Huayu Tian
Retinal neovascularization is one of the most prevalent fundus neovascular diseases, affecting vision and potentially leading to severe complications, such as retinal detachment or irreversible blindness. Current treatments primarily involve intravitreal injections (IVT) of anti-vascular endothelial growth factor (anti-VEGF) agents. However, such treatment often requires repeated injections, develop incomplete responses, and are associated with adverse effects. Therefore, novel therapeutic agents need to be developed that exhibit low side effects and improved therapeutic efficacy of retinal neovascularization. Herein, we develop a novel polymeric gene carrier, phenylboronic acid-modified linear polyethylenimine (LPEI-PBA) that is capable of loading plasmid expressing short hairpin RNA ( p shVEGF), which self-assembles with dexamethasone sodium phosphate (DSP) via electrostatic interactions to form a polymer-based gene-drug co-delivery system ( D SP/L P EI- P BA/ p sh V EGF, DPPV ) for combined neovascularization inhibition. DSP not only exerts anti-inflammatory effects but also enhances the transfection efficiency of LPEI-PBA. DPPV demonstrated favorable anti-neovascular effects both in vitro and in vivo . In an oxygen-induced retinopathy model, a single intravitreal administration of DPPV can significantly inhibited pathological neovascularization, accompanied by the downregulation of glial activation markers glial fibrillary acidic protein (GFAP) and ionized calcium-binding junction molecule 1 (IBA-1), as well as the pro-inflammatory factor interleukin-1β (IL-1β), and the upregulation of the anti-inflammatory factor ARG-1. In conclusion, DPPV nanoparticles effectively inhibit pathological retinal neovascularization through dual anti-inflammation and anti-angiogenesis, showing a promising therapeutic option for fundus neovascularization diseases.
研究领域:
纳米医学
·
基因治疗
·
眼科学
·
药物递送系统
·
炎症研究
✓ 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）