JOURNAL OF NANOPARTICLE RESEARCH
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2014
·Vol. 16
·期 7
·1-14
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IF 2.278
Ma Xiaona,Shu Chang,Guo Jing,Pang Lili,Su Lin,Fu Degang,Zhong Wenying
Abstract A new targeted drug delivery system (DDS) based on oxidized single-wall carbon nanohorns (oxSWCNHs) was developed. Sodium alginate (SA) was used to modify oxSWCNHs to improve its dispersibility and biocompatibility, the first time such a modification to oxSWCNHs was reported. The humanized anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody was bound to the SA as targeting group to selectively kill the tumor cells. Doxorubicin hydrochloride (DOX) was conjugated to oxSWCNHs in basic pH solution by π–π stacking, and its release was triggered by the lower pH as the micro-environment of the tumor. Quantitative analyses showed that the DOX@oxSWCNHs/SA complexes contained 1 g DOX per gram of oxSWCNHs. Cell experiment showed that the DOX@oxSWCNHs/SA-mAb effectively targeted the human breast adenocarcinoma (MCF-7) cells and rarely adhered to the human embryonic kidney 293 (HEK293) cells. And the anticancer effects of the complexes were higher than those of the free DOX. Pharmaceutical efficiency in vivo showed that the relative tumor volumes (RTV) of normal saline (NS) group, oxSWCNH/SA-mAb (2.5 mg/kg) group, DOX (2.5 mg/kg) group, and DOX@oxSWCNHs/SA-mAb (2.5 mg/kg) group were approximately 61, 56, 14, and 7.2, respectively. In addition, higher drug dose (5 mg/kg) of DOX@oxSWCNHs/SA-mAb resulted in a better antitumor activity. Histopathological studies in mice confirmed that the DOX@oxSWCNHs/SA-mAb complexes did not demonstrate any detectable hepatotoxicity, cardiotoxicity, and nephrotoxicity. Graphical abstract
研究领域:
药学
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肿瘤学
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纳米医学
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DOI
高影响因子
TOXICOLOGY LETTERS
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2021
·
IF 4.374
Jiayi Gu,Ling Tong,Xin Lin,Yuming Chen,Hao Wu,Xueling Wang,Dehong Yu
The ototoxic mechanisms of cisplatin on the organ of Corti and spiral ganglion neurons have been extensively studied, while few studies have been focused on the stria vascularis (SV). Herein, we verified the functional and morphological impairment in SV induced by a single injection of cisplatin (12 mg/kg, I.P.), represented by a reduction in Endocochlear Potentials (EP) and strial atrophy, and explored underlying mechanisms. Our results revealed increased extravasation of chromatic tracers (Evans blue dye and FITC-dextran) around microvessels after cisplatin exposure. The increased vascular permeability could be attributed to changes of pericytes (PCs) and perivascular-resident macrophage-like melanocytes (PVM/Ms) in number or morphology, as well as the enhanced level of HIF-1α and downstream VEGF. This capillary leakage led to a high accumulation of cisplatin in the perivascular space in SV, and disrupted the integrity of blood-labyrinth barrier (BLB). Also, tight junction (ZO-1) loosening and Na + , K + -ATPase damage was considered to be other critical contributors of BLB breakdown, which resulted in EP drop and consequent hearing loss. This study explored the role of stria vascularis in cisplatin-induced ototoxicity in terms of BLB hyperpermeability and pointed to a novel therapeutic target for the prevention of cisplatin-related hearing loss.
研究领域:
耳鼻喉科学
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药理学
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毒理学
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DOI
PubMed
高影响因子
Bioengineered
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2021
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IF 3.269
Bo Li,Xianyi Liu,Guogang Wu,Jiawen Liu,Shouliang Cai,Fuxin Wang,Chunyu Yang,Jisheng Liu
Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Materials Today Bio
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2026
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IF 11
Jukai Feng,Yuting Zhang,Wenhan Liu,Pu Zhang,Jianbin Xiao,Qiang Feng,Zhiyu Wang,Jinyu Zhang,Yang Zhong,Zhongying Shi,Meiqi Pan,Xiaolong Zhang,Jingfeng Liu,Jianmin Wang
The combination of atezolizumab (T, anti-PD-L1) and bevacizumab (A, anti-VEGF) (“T+A”) are recommended as first line treatment in patients with unresectable hepatocellular carcinoma (HCC). However, there is a lack of reliable methods to accurately screen beneficiary populations and predict therapeutic outcomes for “T+A” treatment. In this study, we developed two antibody-labelled quantum dot (QD)-based nanoprobes with non-overlapping near-infrared II (NIR-II) fluorescence for simultaneous in vivo imaging of VEGF and PD-L1 levels within tumors. These nanoprobes utilized NIR-II QDs (emission: ∼950 nm and 1550 nm) as cores, while coating with 4-Arm-PEG-NH 2 as a linker to accomplish highly efficient conjugation of anti-VEGF or anti-PD-L1 antibodies via amide condensation. By using tumor-bearing mouse model, we confirmed positive correlation between the in vivo fluorescence signal and the corresponding protein expression level of tumors as determined by immunohistochemistry. Importantly, our results demonstrated that high fluorescence signal of VEGF and PD-L1 levels within tumors indicated more immunosuppressive microenvironment and was associated with faster tumor progression. At meanwhile, fluorescent imaging for VEGF and PD-L1 levels before treatment could predict the endpoint of therapeutic response to “T+A” regimen. Indeed, high fluorescence signal suggested a better therapeutic response versus that with low fluorescence. Overall, our findings established an in vivo dual-targets fluorescent molecular imaging technique as a promising clinical decision-making tool that can predict response to “T+A” regimen in a minimally invasive manner prior to treatment initiation, therapy enabling personalized therapy selection for patients with advanced HCC.
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DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2020
·Vol. 42
·期 7
·1190-1194
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IF 5.064
Shen Zhu-qing,Wang Juan,Tan Wen-fu,Huang Tao-min
Hedgehog plays an important role in a wide range of physiological and pathological conditions. Paracrine activation of Hedgehog pathway in stromal cells increases the expression of VEGF, which promotes neovascularization in colorectal cancer and ultimately the growth of colorectal cancer. Berberine (BBR) has anticancer activity. In this study we investigated whether BBR inhibited the growth of colon cancer through suppressing the paracrine sonic hedgehog (SHH) signaling in vitro and in vivo. We showed that BBR (1–10 μM) dose-dependently inhibited the secretion and expression of SHH protein in HT-29 and SW480 cells. BBR did not influence the transcription of SHH, but promoted the degradation of SHH mRNA, thus decreased the SHH mRNA expression in the colorectal cancer cells. In nude mice bearing HT-29 xenograft, oral administration of BBR (100 mg · kg − 1 · d −1 ) or a positive control drug GDC-0449 (100 mg · kg −1 · d −1 ) for 4 weeks markedly suppressed the growth of HT-29 tumor with BBR exhibiting a better antitumor efficacy. The tumor growth inhibition caused by BBR or GDC-0449 was comparable to their respective inhibitory effect on the mouse-specific Gli mRNA expression in the tumor. However, BBR (20 μM) did not affect the expression of human transcription factor Gli1 mRNA in HT-29 and SW480 cells. In conclusion, BBR promotes the degradation of SHH mRNA in colorectal cancer cells, interrupting the paracrine Hedgehog signaling pathway activity thus suppresses the colorectal cancer growth. This study reveals a novel molecular mechanism underlying the anticancer action of BBR.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2016
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IF 1.931
Shengyan Xi,Lifeng Yue,Mengmeng Shi,Ying Peng,Yangxinzi Xu,Xinrong Wang,Qian Li,Zhijun Kang,Hanjing Li,Yanhui Wang
Chronic liver disease is one of the most common diseases that threaten human health. Effective treatment is still lacking in western medicine. Semen Persicae (Taoren) and Flos Carthami (Honghua) are known to relieve acute hepatic injury and inflammation, improve microcirculation, and reduce tissue fiber. The aim of our study is to investigate the potential mechanisms of Taoren-Honghua Herb Pair (THHP) in murine model of chronic liver disease caused by Carbon Tetrachloride (CCl4). Mice were randomly divided into seven groups: (1) blank, (2) model, (3) control (colchicine, 0.1 mg/kg), (4) THHP (5.53, 2.67, and 1.33 g/kg), and (5) Tao Hong Siwu Decoction (THSWD) (8.50 g/kg). Histological change and microvessels density were examined by microscopy. Hepatic function, serum fibrosis related factors, and hepatic vascular endothelial growth factor (VEGF) were measured with ELISA. VEGF, kinase insert domain-containing receptor (KDR), Flt-1, and Akt mRNA expression in hepatic tissue were determined with PCR. Tissues of Akt, pAkt, KDR, and Flt-1 were measured with western blotting. Data from this study showed that THHP improved hepatic function and restrained the hepatic inflammation and fibrosis. Its role in inhibiting pathological angiogenesis and hepatic fibrogenesis may be through affecting the angiogenesis-associated VEGF and its upstream and downstream signaling pathways.
研究领域:
药理学
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肝病学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
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2024
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IF 4.2
Jianying Tan,Huanran Wang,Sainan Liu,Li Li,Hengquan Liu,Tao Liu,Junying Chen
Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn 2+ ) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn 2+ were loaded into heparin and poly- l -lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo . Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.
研究领域:
生物材料
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心血管工程
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组织工程
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纳米技术
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DOI
PubMed
高影响因子
Biomaterials Advances
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2022
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IF 0
Lianghua Jiang,Xufeng Yang,Yijian Zhang,Dawei He,Yijun Gao,Ke Lu,Yanming Hao,Yan Gao,Daming Lu,Xiangyun Jin,Chong Li
Accelerating angiogenesis of diabetic wounds is crucial to promoting wound healing. Currently, vascular endothelial growth factor (VEGF), an angiogenesis-related bioactive molecule, is widely used in clinic to enhance wound angiogenesis, but it faces problems of inactivation and low utilization due to harsh microenvironment. Here, we developed a novel reactive oxygen species (ROS)-scavenging hydrogel aimed to polarize macrophages toward an anti-inflammatory phenotype, inducing efficient angiogenesis in diabetic wounds. This composite hydrogel with good biosafety and mechanical properties showed sustainable release of bioactive VEGF. Importantly, it could significantly reduce ROS level and rapidly improve wound microenvironment, which ensured the activity of VEGF in vitro and in vivo and successful healing eventually. At the same time, the composite hydrogel exhibited excellent antibacterial properties. In vivo results confirmed good anti-inflammatory, stimulated vascularization and accelerated wound healing attributed to the novel ROS-scavenging hydrogel, which might serve as a promising wound dressing in diabetic wound healing.
研究领域:
生物医学工程
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伤口愈合
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材料科学
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药剂学
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产品关联
DOI
PubMed
GYNECOLOGICAL ENDOCRINOLOGY
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2022
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IF 2.277
Jie Zhang,Jie Huang,Xinhuan He,Ning Li,Yu Miao,Beiqing Li,Xiaoguang Shao,Ningning Wang
Aims Ginkgo biloba extract (EGb) has been widely applied in the treatment of cerebrovascular and neurological diseases. However, the effect of EGb761 on ovarian hyperstimulation syndrome (OHSS), a vascular disorder and life-threatening complication of in vitro fertilization and intracytoplasmic sperm injection therapy (IVF/ICSI), has not been evaluated.Materials and methods Forty female Wistar rats aged 22-days old (D22) were divided into eight groups: Control rats received intraperitoneal injection of saline for five consecutive days (D22–D26); OHSS model group received 10 IU equine chorionic gonadotropin (eCG) for four consecutive days (D22–D25) and 30 IU of human chorionic gonadotropin (hCG) on the 5th day (D26); Prophylactic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/day) 1 h before injection of eCG (hCG) for seven consecutive days; Therapeutic treatment group received three doses of EGb761 (50, 100, and 200 mg/kg/day) 48 h after injection of eCG (hCG) for seven consecutive days.Results All three doses of EGb761 therapeutic medication significantly reduced ovarian mass index of OHSS model rats (p ≤ .01). Furthermore, therapeutic treatment group exhibited improved vascular permeability, decreased estradiol and progesterone levels, lower corpus luteum, and higher follicle numbers compared with the OHSS model. Elevated protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) in both ovary and kidney of the OHSS model was restrained by EGb761 therapeutic treatment.Conclusions EGb761 therapeutic medication decreases vascular permeability in OHSS rat model by inhibiting VEGF and VEGFR expression, which may contribute to the treatment of OHSS.
研究领域:
生殖医学
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药理学
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血管生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2026
·
IF 5.2
Xiumei Liu,Zi Yan,Jing Li,Hong Zou,Haoyue Zhong,Peixin Lee,Yaqi Lyu,Nianping Feng
First study of LB-Exos in modulating ocular disease. • LB-Exos present as natural, multi-target nanotherapeutics for diabetic retinopathy. • LB-Exos protect against oxidative stress, restore blood-retinal barrier integrity. • LB-Exos downregulate the HIF-1α/VEGF/VEGFR2 axis. • LB-Exos exhibit synergistic effect with standard anti-VEGF therapy. The growing interest in plant-derived extracellular vesicles (EVs) as nanotherapeutics has positioned Lycium barbarum L. EVs (LB-Exos) as a promising candidate for treating diabetic retinopathy (DR), a condition characterized by pathological angiogenesis and blood-retinal barrier (BRB) dysfunction. This study investigates the multifaceted therapeutic effects of LB-Exos, isolated from fresh goji berries and characterized for their bioactive metabolite cargo. In vitro, LB-Exos protected ARPE-19 cells from apoptosis by modulating the MAPK pathway and the Bcl-2/BAX/caspase-3 axis. In HUVECs, LB-Exos suppressed angiogenesis by downregulating the HIF-1α/VEGF/VEGFR2 axis and ANGPT2, showing synergistic effects with the standard therapy of bevacizumab (BVZ). These mechanisms were validated in a streptozotocin-induced diabetic mouse model, where LB-Exos treatment alleviated retinal pathology, reduced neovascularization, and restored BRB integrity by upregulating tight junction proteins. Our study establishes LB-Exos as a novel, natural nanoplatform that concurrently targets multiple pathological pathways in DR. This work elucidates the multifaceted therapeutic potential of PDEVs in ophthalmology and highlights their complementary mechanism to enhance current anti-VEGF therapy. Download: Download high-res image (321KB) Download: Download full-size image
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高影响因子
Biofabrication
·
2025
·Vol. 18
·期 1
·015010
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IF 8
Xuan Jiao,Kexun Liu,Jie Wu,Peian Cai,Limeng Chao,Chang Liu,Kegong Chen,Xionghai Qin,Xin Tian,Yuanzhong Zhao,Hai Tian,Wei Chen
The transplantation of human bone marrow mesenchymal stem cells (hMSCs) exhibits promising therapeutic effects in the treatment of myocardial infarction (MI), however, its clinical application is limited due to the low survival rate of the transplanted cells. Three-dimensional (3D) bioprinted tissue engineering patches have demonstrated efficacy as a delivery approach to enhance the viability and engraftment of stem cells. In this study, we have developed a novel hMSCs tissue-engineered patch equipped with a nano-slow-release system using 3D bioprinting technology. The patch is based on a matrix material consisting of methacrylated gelatin (GelMA) and chitosan nanoparticles loaded with vascular endothelial growth factor (VEGF), which possesses pro-angiogenic effects. The resulting patch demonstrated excellent compatibility with hMSCs and enabled stable, sustained VEGF release. In vivo results showed that the patch significantly reduced cardiomyocyte apoptosis three days after MI, and improved cardiac function and myocardial fibrosis at 28 d post-surgery. These effects were closely associated with the patch’s potent angiogenic properties and favorable stem cell survival. In conclusion, this study successfully developed a 3D-printed tissue engineering patch with strong potential for clinical application, offering a promising new approach for the treatment of MI.
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高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Ya-wei Zhang,Xiaoyang Pang,Yan Yang
Background A new spray adhesive (KYNA-PF127) was established through the combination of thermosensitive hydrogel (Pluronic F127) and KYNA, aimed to investigate the effect of KYNA-PF127 on multi-territory perforator flaps and its possible molecular mechanism. Materials and methods 36 SD male rats with 250–300 g were randomly divided into 3 groups (n = 12): control group, blank glue group and KYNA-PF127 group. KYNA-PF127 hydrogel was prepared and characterized for its morphology and properties using scanning electron microscopy. CCK-8 assay, scratch wound assay, transwell assay, tube formation assay and Ki67 staining were used to study the effect of KYNA-PF127 on the proliferation, migration, and tube formation of HUVECs. VEGF and FGF2 were measured by qPCR to evaluate the angiogenesis capacity of HUVECs in vitro. In vivo, the effect of each group on the survival area of the cross-zone perforator flap was evaluated, and angiogenesis was evaluated by HE and immunofluorescence (CD31 and MMP-9). The effect of inflammation on skin collagen fibers was assessed by Masson. Immunohistochemistry (SOD1, IL-1β, TNF-α) was used to evaluate the effects of oxidative stress and inflammatory factors on multi-territory flaps. Results KYNA-PF127 has good sustained release and biocompatibility at 25% concentration. KYNA-PF127 promoted the proliferation, migration, and angiogenesis of HUVECs in vitro. In vivo, the survival area of multi-territory perforator flaps and angiogenic capability have increased after KYNA-PF127 intervention. KYNA-PF127 could effectively reduce the oxidative stress and inflammation of multi-territory perforator flaps. Conclusion KYNA-PF127 promotes angiogenesis through its antioxidant stress and anti-inflammatory effects, and shows potential clinical value in promoting the survival viability and drug delivery of multi-territory perforator flaps.
研究领域:
生物医学工程
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组织工程
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药学
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分子生物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）