RSC Advances
·
2019
·Vol. 9
·期 21
·12110-12123
·
IF 3.049
Liu-Qing Gu,Peng-Fei Cui,Lei Xing,Yu-Jing He,Xin Chang,Tian-Jiao Zhou,Yu Liu,Ling Li,Hu-Lin Jiang
Multi-drug resistance (MDR) of tumor cells has greatly hindered the therapeutic efficacy of chemotherapeutic drugs, resulting in chemotherapy failure, while overexpression of ATP-binding cassette (ABC) transporters in cell membranes is the leading cause of MDR. In this study, we reported novel self-assembled triphenylphosphine-quercetin–polyethylene glycol–monoclonal antibody nanoparticles (TQ–PEG–mAb NPs) for overcoming MDR primarily through mitochondrial damage to block ATP supply to ABC transporters both in vitro and in vivo. The doxorubicin (DOX)-loaded NPs (TQ/DOX–PEG–mAb) were composed of two drugs (TQ and DOX) and an outer shielding shell of the PEG–mAb conjugate. Besides, the outer shell could be acid-responsively detached to expose the positive charge of TQ inside the NPs to enhance cellular uptake. TQ was proved to effectively induce mitochondrial damage with increased ROS levels and depolarization of mitochondrial membrane potential (MMP), leading to prominently reduced ATP supply to ABC transporters. Moreover, the involvement of the anti-vascular endothelial growth factor (VEGF) mAb was not only for efficient targeting but also for combined therapy. Consequently, TQ/DOX–PEG–mAb showed that the internalized amount of DOX was largely improved while the efflux amount was dramatically inhibited on MCF-7/ADR cells, indicating excellent reversal of DOX resistance. Importantly, the growth of DOX-resistant breast tumors was significantly inhibited with no evident systemic toxicity. Therefore, the employment of TQ–PEG–mAb is believed to be a new approach to improve the efficacy of chemotherapeutic drugs in MDR tumors.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Fang Yang,Xueyang Fang,Wenting Jiang,Tianfeng Chen
With many desirable features, such as being more effective and having multiple effects, antiangiogenesis has become one of the promising cancer treatments. The aim of this study was to design and synthesize a new targeted bioresponsive nanosystem with antiangiogenesis properties. The mUPR@Ru(POP) nanosystem was constructed by the polymerization of Ulva lactuca polysaccharide and N-isopropyl acrylamide, decorated with methoxy polyethylene glycol and Arg–Gly–Asp peptide, and encapsulated with anticancer complex [Ru(phen)2p-MOPIP](PF6)2·2H2O. The nanosystem was both pH responsive and targeted. Therefore, the cellular uptake of the drug was greatly improved. Moreover, the mUPR@Ru(POP) had strong suppressive effects against vascular endothelial growth factor (VEGF)-induced angiogenesis through apoptosis. The mUPR@Ru(POP) significantly inhibited VEGF-induced human umbilical vein endothelial cell migration, invasion, and tube formation. These findings have presented new insights into the development of antiangiogenesis drugs.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2026
·
IF 11.8
Xi Jiang,Fengqi Yang,Huiling Gong,Yanfei Mou,Junyi An,Lei Wang,Xiaona Wang,Zhenzhen Zhang,Xiao Wei,Li Sun,Wenli Wang,Fenglei Cao,Yang Zhao,Ding Qu
Wet age-related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), faces a clinical challenge of diminishing efficacy during long-term anti-VEGF monotherapy. An AI-assisted analytical framework pinpointed impaired retinal pigment epithelium (RPE) autophagy and a pro-inflammatory microenvironment driven by retinal microglia-recruited monocytes as co-conspirators in CNV progression. To tackle these dual culprits, we developed an intravitreal injectable hydrogel (Rab&BCL-M@G) that co-encapsulates ranibizumab (Rab) and a small-sized baicalin-loaded microemulsion (BCL-M), enabling controlled and sustained co-delivery of both agents to the retina for over 14 days. Guided by the AI-identified targets, we demonstrated that baicalin promoted dysfunctional mitochondria clearance via the AKT2-PGC-1α-mediated autophagic flux and suppressed monocyte recruitment by disrupting microglial CCL4 signaling. This two-pronged action ameliorated inflammation and angiogenesis, synergizing with Rab. In a laser-induced wAMD mouse model, a single intravitreal injection of Rab&BCL-M@G sustainably reduced CNV area, promoted repair, restored autophagy, and diminished microglial infiltration. Crucially, subsequent wet-lab validation confirmed a positive pathological correlation among defective autophagy, inflammation, and angiogenesis, thereby closing the loop from computational prediction to experimental verification and explaining suboptimal long-term performance after Rab monotherapy. This study proposes a promising synergistic strategy, advancing wAMD therapy through precision delivery and AI-informed mechanism discovery.
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Guirong Zheng,Ruirui Zhao,Aixiao Xu,Zhichun Shen,Xian Chen,Jingwei Shao
Combination with chemotherapeutic drug and gene therapy has been proven highly effective in suppressing tumor progression. Hence, an asialoglycoprotein receptor (ASGPR)-targeting nanodrug delivery system based on mesoporous silica (MSN) nanocarrier for co-delivery of sorafenib (SO) and vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) to hepatocellular carcinoma (HCC) was successfully designed and synthesized. The structure of nanoparticles was characterized by IR, particle size, zeta potential and N2 adsorption-desorption. The nanoparticles were further evaluated for drug release, cellular uptake, transfection, cell cytotoxicity and cell cycle against HepG2 and Huh7 cells. In vitro testing demonstrated that MSN-LA delivery system could not only induce S cell cycle arrest, enhance the cytotoxicity and improve the tumor target of SO and siVEGF, but also enhance the siVEGF transfection efficiency in ASGPR-overexpressing Huh7 cells. Overall, the MSN-LA delivery system can be a promising drug carrier which could further enhance the anti-cancer efficacy of SO and siVEGF via the active targeting property of LA .
研究领域:
药剂学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIVER INTERNATIONAL
·
2025
·Vol. 45
·期 3
·e70024
·
IF 5.2
Guqing Luo,Zhenghao Wu,Qiang Fan,Chihao Zhang,Jiayun Lin,Hongjie Li,Jinbo Zhao,Haizhong Huo,Xiaoliang Qi,Guangbo Wu,Min Chen,Jiwei Yu,Lei Zheng,Meng Luo
Background and Aims Lymphangiogenesis is enhanced during the development of liver cirrhosis and portal hypertension (PHT). However, hepatic lymphatic vascular system is understudied in liver cirrhosis and PHT. Hydrogen sulfide (H 2 S) and related compounds have potential prolymphangiogenic effects besides its previously reported vascular-protective effects. Therefore, we aimed to investigate the effects of endogenous H 2 S donor S-allyl-cysteine (SAC) on bile duct ligation (BDL)-induced liver cirrhosis and PHT. Methods BDL rats with cholestatic liver cirrhosis and PHT were orally administrated with SAC at 100 or 200 mg/kg/day, as well as DL-propargylglycine (PAG) or MAZ-51 injections. Hemodynamic parameters were determined, and subsequent evaluations of liver fibrosis, intrahepatic vascular resistance (IHVR) and lymphangiogensis were performed. Human lymphatic endothelial cells (hLECs) were used for in vitro verification of prolymphangiogenic effects of SAC. Results SAC treatment significantly decreased PP and promoted endogenous H 2 S production. Liver fibrosis and IHVR were also ameliorated. Hepatic and mesenteric lymphangiogenesis were enhanced in BDL rats and further promoted by SAC despite a significant downregulation of hepatic VEGF-C. Inhibition of H 2 S production by PAG significantly reduced lymphatic vessels, while inhibition of lymphangiogensis by MAZ-51 reversed the protective effects of SAC against PHT. SAC enhanced lymphangiogenic functions in vitro by promoting cellular H 2 S production and activating Akt phosphorylation without altering VEGF-C/D, which were reversed by PAG and MAZ-51. Conclusions SAC significantly alleviated BDL-induced liver cirrhosis and PHT. Meanwhile, elevated H 2 S induced by SAC facilitated lymphangiogenesis via a VEGF-C-independent manner, which contributed to the alleviation of PHT.
研究领域:
医学
·
药理学
·
肝脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Yan-Wen Ding,Yang Li,Zhi-Wei Zhang,Jin-Wei Dao,Dai-Xu Wei
Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.
研究领域:
药学
·
生物医学工程
·
皮肤科
·
材料科学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Xiaotian Gao,Xiaoniao Chen,Luying Qiao,Yingtao Zhang,Xiaoling Liu,Sifan Yang,Yan Zheng,Xun Chen,Xu Wang,Ran Liu,Zheyi Dong,Qian Wang,Quan Hong
Ethnopharmacological relevance Formononetin (FMN) is a natural isoflavone found in several medicinal plants. Its effects on diabetic retinal and renal microvascular injury and EGR1/VEGF-related endothelial responses remain incompletely defined. Aim of the study To assess whether FMN attenuates early diabetes-associated retinal and renal injury and whether EGR1 is involved. Materials and methods Alloxan-induced diabetic rabbits received FMN orally at 25 mg/kg/day from Week 4 to Week 16 after pretreatment renal and OCT/OCTA assessment. Renal function, histopathology, retinal flat mounts, longitudinal OCTA, and tissue EGR1/VEGF expression were examined. High-glucose-treated retinal, renal microvascular, and umbilical vein endothelial cells were used for functional assays. EGR1 overexpression, VEGFA promoter reporter assays, SPR, docking, and molecular dynamics simulations were also performed. Results FMN lowered serum creatinine, blood urea nitrogen, and urinary albumin-to-creatinine ratio, and reduced renal histopathological injury. It also attenuated retinal capillary loss, retinal thinning, and OCTA abnormalities despite persistent hyperglycemia. Retinal and renal tissues from FMN-treated rabbits showed lower EGR1 and VEGF expression. In endothelial cells, FMN reduced EGR1 and VEGF expression, abnormal tube formation, permeability, invasion, ROS, and inflammatory mediator release, while increasing NO-related signals. EGR1 overexpression weakened several effects and increased VEGFA promoter activity through the predicted EGR1-binding sequence. SPR detected FMN–EGR1 binding with a K_D of 3.245 μM. Computational analyses provided structural context. Conclusions FMN attenuated early diabetes-associated retinal and renal injury and was linked to EGR1/VEGF-related endothelial responses. The data support EGR1 involvement but do not establish it as the sole target or mediator of FMN.
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产品关联
DOI
高影响因子
Brazilian Journal of Cardiovascular Surgery
·
2015
·Vol. 30
·期 2
·159-163
·
IF 0.55
Song Chun-Li,Li Qian,Yu Yun-Peng,Wang Guan,Wang Jin-Peng,Lu Yang,Zhang Ji-Chang,Diao Hong-Ying,Liu Jian-Gen,Liu Yi-Hang,Liu Jia,Li Ying,Cai Dan,Liu Bin
Introduction: Intravascular coronary stenting has been used in the treatment of coronary artery disease (CAD), with a major limitation of in-stent restenosis (ISR). The 316 stainless steel has been widely used for coronary stents. In this study, we developed a novel coating method to reduce ISR by simultaneously coating vascular endothelial growth factor (VEGF) and anti-CD34 antibody on 316L stainless steel. Methods: Round 316L stainless steel sheets in the D-H group were polymerized with compounds generated from condensation reaction of dopamine and heparin using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). Sixteen sheets from the D-H group were further immersed into 1ug/ml VEGF165 and 3mg/ml heparin sodium one after another for 10 times, and named as the D-(H-V)10 group. Eight sheets from the D-(H-V)10 group were coated with anti-CD34 antibody and termed as the D-(H-V)10-A group. Immunofluorescence assay and ELISA were used to evaluate whether the 316L stainless steel disks were successfully coated with VEGF and anti-CD34 antibody. Results: The results of immunofluorescence assay and ELISA showed that VEGF could be detected in the D-(H-V)10 and D-(H-V)10-A group, suggesting the steel sheets were successfully covered with VEGF. Anti-CD34 antibody could only be observed in the D-(H-V)10-A group, which was the only group coated with CD34 antibody. Both results suggested that the 316L stainless steel sheets were successfully coated with VEGF and anti-CD34 antibody. Conclusion: Our study developed a method to simultaneously coat VEGF and anti-CD34 antibody to stainless metal steel. This research serves as a fundamental role for a novel coating strategy.
研究领域:
心血管工程
·
生物材料
·
医疗器械
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2024
·Vol. 29
·期 1
·1-11
·
IF 2.8
Armaghan Muhammad,Khan Khushbukhat,Irfan Muhammad,Hafeez Amna,Zafar Sameen,Javed Zeeshan,Sharifi-Rad Javad,Butnariu Monica,Sarac Ioan,Bagiu Iulia-Cristina,Bagiu Radu Vasile
Scientists have been compelled to search for alternative treatments due to the increasing prevalence of chemoresistance as well as the agonising and distressing side effects of both chemotherapy and radiation. Plant extracts have been exploited to treat various medical conditions for ages. Considering this fact, the main focus of various recent studies that are being conducted to find new and potent anticancer drugs involves the identification and utilisation of potential therapeutic chemicals present in plant extracts. Koetjapic acid (KJA), which belongs to the family of triterpenes, is primarily isolated from Sandoricum koetjape . Ongoing investigations into its therapeutic applications have revealed its tendency to impede the growth and proliferation of cancer cells. Koetjapic acid activates the intrinsic apoptotic pathway and promotes the death of cancer cells. Moreover, it inhibits angiogenesis and the dissemination of tumour (metastasis) by targeting the VEGF signalling cascade. Therefore, this study aims to elucidate the underlying mechanism of anticancer activity of koetjapic acid, providing significant insight into the compound’s potential as an anticancer agent.
研究领域:
药理学
·
肿瘤学
·
植物化学
✓ 已验证
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Kai Dong,Hengyu Lei,Jian Kang,Xue Leng,Ruirui Ma,Danyang Wang,Qingyuan Zhou,Jie Yu,Tingli Lu,Jianfeng Xing
The oxygen-consuming property of photodynamic therapy (PDT) affects its effects and aggravates tumor hypoxia, thus upregulating the vascular endothelial growth factor (VEGF) to exacerbate tumor metastasis and lead to treatment failure. Therefore, it is necessary to monitor the dynamic changes in the factors related to PDT and tumor development trends in real time, thus helping to improve PDT efficiency. This study fabricated a fluorescent probe, TPE-2HPro, and a fluorescein-labeled aptamer probe, FAM-AptamerVEGF, to detect hydrogen peroxide (H2O2) and VEGF through the photoinduced electron-transfer effect and the specific affinity of the aptamer to VEGF, respectively. The two probes were loaded into the inner pores and absorbed on the surface of polydopamine coating-wrapped mesoporous silica nanoparticles (MSN@PDA) to construct the dual-probe-loaded system, MSNTH@PDAApt, which was kept stable in fetal bovine serum (FBS) solution and achieved pH-responsive release behavior, thus helping to increase the accumulation of the two probes in tumor cells. The dichloroacetic acid-mediated in vitro antitumor tests showed that the changing trends of H2O2 and VEGF levels were consistent with the results of related mechanism studies and could be monitored by MSNTH@PDAApt. The in vitro chlorin e6 (Ce6)-mediated PDT treatment demonstrated that when the illumination condition was 650 nm, 50 mW/cm2 for 10 min, cells were more inclined to metastasis and invasion rather than death due to a substantial increase in VEGF expression at the low Ce6 concentrations. With the increase of the Ce6 concentration, the growth of the H2O2 level gradually exceeded that of VEGF, and the reactive oxygen species (ROS)-mediated cell death dominated when the Ce6 concentration was about 2 times its IC50 values. Besides, hypoxia also affected the H2O2 and VEGF changes. These results demonstrated that MSNTH@PDAApt could precisely monitor and assess the tumor development trends during PDT treatment, thus helping improve the treatment effect.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Express
·
2023
·Vol. 13
·期 2
·312-315
·
IF 0.7
Pan Jie,Cui Liang,Liu Si-Han
Lung cancer is currently the most common malignant tumor and most lethal cancer worldwide, posing a serious threat to human life and health. Mitomycin has been widely used in the clinical treatment of malignant tumors owing to its strong antitumor effects. In this study, hyaluronic
acid/carboxymethyl chitosan hydrogels loaded with mitomycin were prepared by chemical synthesis. The SEM results showed that the hydrogels had a 3D interoperable porous structure, which facilitates drug loading. Biological experiments showed that the mitomycin-loaded hydrogels remarkably reduced
the viability of cancer cells and inhibited the activation of the VEGF signaling pathway in cancer cells in a dose-dependent manner. Thus, the hydrogels are expected to be used as a drug carrier material for lung cancer treatment.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOCHEMICAL ANALYSIS
·
2025
·
IF 2.6
Jing Xu,Yulong Zhu,Yi Wei,Peirong Gan,Shilin Xia,Ya Li,Xiaoman Jiang,Yan Wang,Hong Wu
Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily manifests with symptoms such as heat and toxin. However, the key components and molecular mechanisms of Zhizi Baipi decoction (ZBD) in the treatment of RA are still unclear. Objectives The study aimed to explore the mechanism of action of ZBD for treating RA through ingredient analysis, network pharmacology, and experimental validation. Material and Methods The chemical constituents of ZBD were identified by ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS E ). Additionally, the active ingredients of ZBD treating RA were screened by network pharmacology and using molecular docking to verify the binding energy of the active ingredients and ZBD's targets. Then we elucidated ZBD's mechanism of action on collagen-induced arthritis (CIA) model rats. Subsequently, experimental validations were used to validate the findings of network pharmacology. Results A total of 84 chemical constituents was identified by UPLC-Q-TOF-MS E . The results of network pharmacology indicated that ZBD could exert its therapeutic effect on RA through the vascular endothelial growth factor (VEGF) pathway. Molecular docking revealed a strong binding capacity between the target KDR and the active ingredients. Additionally, we quantified the five active ingredients of ZBD. In vivo experiments demonstrated that ZBD inhibited synovial angiogenesis and alleviated the occurrence and progression of RA. Conclusion Overall, ZBD has a significant therapeutic effect on RA. The results of qualitative analysis, network pharmacology, molecular docking, and in vivo experiments indicated that the main active components of ZBD could modulate the VEGF pathway to treat RA.
研究领域:
药理学
·
免疫学
·
分子生物学
·
中医
✓ 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）