NEW JOURNAL OF CHEMISTRY
·
2018
·Vol. 42
·期 14
·11565-11572
·
IF 3.201
Tao Wang,Guorong Jia,Chao Cheng,Qiuhu Wang,Xiao Li,Yanyan Liu,Chaofan He,Luguang Chen,Gaofeng Sun,Changjing Zuo
Multimodal imaging can improve the accuracy of cancer diagnosis by combining two or more imaging modalities into one system. In this study, PEGylated BaGdF5 nanoparticles (NPs) were synthesized by a hydrothermal method, and the formed PEG-BaGdF5 NPs showed good X-ray attenuation properties and positive MR contrast effects in vitro. Considering that the overexpression of integrin αvβ3 in the endothelial cells of angiogenic tumor vasculature is universal, RGD peptide, which can recognize and bind integrin αvβ3 specifically, was connected to the surface of PEG-BaGdF5 NPs. The resulting RGD-PEG-BaGdF5 NPs had good biocompatibility and a long half-life in vivo. In VX2 tumor-bearing mice, the HU values and MR signal enhancement of tumor sites in the targeted group were both higher than that in the non-targeted group after intravenous injection of RGD-PEG-BaGdF5 NPs or PEG-BaGdF5 NPs, respectively. Therefore, the RGD-PEG-BaGdF5 NPs may be used as dual-modal CT/MR contrast agents of different types of solid tumors via an active RGD-mediated vasculature targeting pathway.
研究领域:
医学影像
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纳米技术
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肿瘤学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 30
·6338-6346
·
IF 4.726
Hao Hu,Yuanyuan You,Lizhen He,Tianfeng Chen
Angiogenesis is essential for tumorous progression and metastasis. The RGD (Arg–Gly–Asp acid) peptide has been demonstrated to be a remarkable targeting reagent and can be distinguished by the integrin receptor overexpressed in various human tumor cells. Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers applied for delivery of drugs or genes. It is well known that NAMI-A is an excellent drug for antimigration of tumor cells. Targeting the tumor vasculature with RGD-modified nanomaterials is expected to be a promising strategy for cancer therapy. Herein we have investigated the antiangiogenic activity of NAMI-A-loaded and RGD peptide surface decorated mesoporous silica nanoparticles in vitro and in vivo. The results revealed that NAMI-A@MSN-RGD remarkably enhanced the cellular uptake and antiangiogenic efficacy in contrast to bare NAMI-A in vitro. The nanosystem of NAMI-A@MSN-RGD also exhibited inspiring antiangiogenic action in vivo. Furthermore, the RGD-functionalized nanodrug inhibited angiogenesis by means of apoptosis by triggering ROS-mediated DNA damage in human umbilical vein endothelial cells (HUVECs). Our results suggested that the use of RGD-peptide modified MSNs as a vehicle of anticancer drugs is an efficient way to construct cancer-targeted nanosystems with antiangiogenic activity.
研究领域:
药学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2024
·Vol. 86
·期 1
·e70043
·
IF 3.5
Qingqing Li,Yufeng Liu,Yilin Cheng,Huaibao Cao,Kunda Du,Tianyu Zhu,Defeng Xu,Hang Hu
Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug docetaxel (DTX). Peptide–drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. In the present research, DTX is condensed with 3-(pyridin-2-yldisulfanyl) propanoic acid via ester bond to obtain the intermediate Py-SS-DTX. Two conjugates GSS-DTX and RGDC-SS-DTX were obtained by conjugation of Py-SS-DTX with glutathione (GSH) and RGDC peptide through a thiol-disulfide exchange reaction. Afterwards, these two peptide–DTX conjugates were characterized by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. The GSS-DTX and RGDC-SS-DTX were further evaluated in terms of drug release, cell cycle inhibition, cell apoptosis, and cytotoxicity. The results show that both the GSS-DTX and RGDC-SS-DTX exhibit reduction-responsive drug release and RGDC-SS-DTX exhibit higher reduction-responsiveness. The in vitro antitumor activity study shows that RGDC-SS-DTX exhibits enhanced G2/M phase arrest, cell apoptosis rate, and cytotoxicity as compared to GSS-DTX and free DTX. Besides, RGDC-SS-DTX shows reduced cytotoxicity on normal cells as compared to free DTX. The RGDC-SS-DTX synthesized in this study represents a novel DTX conjugate to effectively and selectively inhibit tumor cells.
研究领域:
药学
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肿瘤学
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生物化学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2018
·
IF 2.829
Boyi Niu,Yixian Zhou,Ting Wen,Guilan Quan,Vikramjeet Singh,Xin Pan,Chuanbin Wu
Packaging enough genetic materials is necessary for gene delivery, but functional modification of the carriers may affect their gene loading capacity. In this study, RGD peptide-modified mesoporous silica nanoparticles were synthesized to investigate the influences of functionalization on their DNA adsorption and desorption behaviors. Effects of the functionalization degree of the nanocarriers and the adsorption conditions including DNA concentration, pH, ionic strength and temperature were studied. The DNA adsorption of the nanocarriers were enhanced by reducing pH or adding moderate amounts of ionic salt. Compared with nonfunctional nanoparticles, nanoparticles with low degree of functionalization possessed decreased DNA adsorption capacity but increased adsorption stability. High degree of functionalization resulted in both poor adsorption capacity and stability. Systematic studies showed that the adsorption processes were spontaneous and endothermic, and could be well described by pseudo-second-order kinetic model , Langmuir and Freundlich models. In summary, the DNA loading capacity of mesoporous silica nanoparticles can be improved by proper functionalization and optimized adsorption conditions.
研究领域:
生物材料学
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分子生物学
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纳米医学
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产品关联
DOI
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2019
·Vol. 17
·期 15
·3853-3860
·
IF 3.49
Leixia Mei,Keming Xu,Ziran Zhai,Suyun He,Tingting Zhu,Wenying Zhong
Drug incorporation in hydrogels often brings undesirable effects on the stability or mechanical properties of the system. To address this problem, we report the design and synthesis of a RGD-derived peptide conjugate (1-RGDH) for its co-assembly with a commonly used chemotherapeutic drug, doxorubicin (DOX), that formed electrostatic interactions with the 1-RGDH peptide and reinforced the supramolecular network of nanofibers within the matrix of the hydrogel. The hybrid hydrogel demonstrated excellent viscoelastic and shear-thinning properties that greatly facilitated the development of injectable drug delivery systems. Furthermore, it demonstrated a unique pH responsive release of DOX under weakly acidic conditions, paving ways for the controlled release of drug cargos in a typical tumor microenvironment with mild acidity. Finally, the DOX-incorporated hydrogel exhibited a superior anti-tumor efficacy in non-small-cell lung cancer cells A549 compared to the aqueous solution of free DOX, with an integrin receptor-mediated endocytosis pathway revealed for the cellular uptake of DOX-incorporated nanofibers.
研究领域:
药物递送系统
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生物材料
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 1
·276
·
IF 5.4
Xuanping Zhao,Chuan Liu,Zichao Wang,Yingyuan Zhao,Xuyang Chen,Haizhen Tao,Hong Chen,Xueqin Wang,Shaofeng Duan
Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it is still of great clinical significance to develop highly efficient therapies with few side effects for the treatment of hepatocellular carcinoma. Herein, we developed a highly effective nanocarrier, cyclic RGD peptide-conjugated magnetic mesoporous nanoparticles (RGD[email protected]NPs), to deliver the chemotherapeutic drug doxorubicin (DOX) to human hepatocellular carcinoma HepG2 cells, and further explored their synergistic apoptosis-promoting effects. The results showed that the preparedRGD[email protected]NPs had good stability, biosafety and drug-loading capacity, and significantly improved the absorption of DOX by HepG2 cells, and that theRGD[email protected]@DOX NPs could synergistically promote the apoptosis of HepG2 cells. Thus, this cyclic RGD peptide-modified magnetic mesoporous silicon therapeutic nanosystem can be regarded as a potentially effective strategy for the targeted treatment of hepatocellular carcinoma.Keywords:cyclic RGD peptide;anticancer drug delivery;targeted nanoparticles;hepatocellular carcinoma;apoptosis
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ANNALS OF BIOMEDICAL ENGINEERING
·
2020
·Vol. 48
·期 5
·1511-1523
·
IF 3.324
Ding Yilei,Zhao An-sha,Liu Tianmei,Wang Ya-nan,Gao Yuan,Li Jing-an,Yang Ping
In this contribution, an injectable hydrogel was developed with chitosan, gelatin, β-glycerphosphate and Arg-Gly-Asp (RGD) peptide: this hydrogel is liquid in room temperature and rapidly gels at 37 °C; RGD peptide promises better growth microenvironment for various cells, especially endothelial cells (EC), smooth muscle cells (SMC) and mesenchymal stem cells (MSC). Both stromal cell-derived factor-1 (SDF-1) nanoparticle and vascular endothelial growth factor (VEGF) nanoparticles were loaded in the injectable hydrogel to simulate the natural nanoparticles in the extracellular matrix (ECM) to promote angiogenesis. In vitro EC/SMC and MSC/SMC co-culture experiment indicated that the nanocomposite hydrogel accelerated constructing embryonic form of blood vessels, and chick embryo chorioallantoic membrane model demonstrated its ability of improving cells migration and blood vessel regeneration. We injected this nanocomposite hydrogel into rat myocardial infarction (MI) model and the results indicated that the rats heart function recovered better compared control group. We hope this injectable nanocomposite hydrogel may possess wider application in tissue engineering.
研究领域:
生物材料学
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再生医学
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心血管研究
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组织工程
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Yan Huijie,You Yun,Li Xinjian,Liu Lei,Guo Fengqian,Zhang Qiongling,Liu Dewen,Tong Yan,Ding Shilan,Wang Jinyu
Pharmacological Relevance: Paclitaxel (PTX) is currently the only botanical drug that can control the growth of cancer cells. Paclitaxel is widely used in the treatment of breast cancer, ovarian cancer, uterine cancer, non-small cell lung cancer and other cancers.Aim: Folate receptor and integrin αvβ3 are highly expressed on the surface of human breast cancer cells MCF-7. Folic acid and arginine-glycine-aspartate (Arg-Gly-Asp, RGD) tripeptide sequence have a high affinity for folate receptor and integrin αvβ3, respectively. To enhance the effect on breast cancer, we constructed the folate acid and RGD peptide dual-targeted (MSNs-NH2-FA-RGD) drug-carrier based on mesoporous silica nanoparticles.Methods: The structure of mesoporous nanocarriers was characterized by Fourier transform infrared spectroscopy, nitrogen adsorption-desorption analysis, transmission electron microscopy, laser particle size analyzer, and thermogravimetric analysis. Paclitaxel was chosen as the model drug. The targeting-ability was verified by observing the uptake of mesoporous carriers loaded with rhodamine in MCF-7, MCF-10A, and HeLa cells using a fluorescence microscope. The cytotoxicity of the blank carrier MSNs-NH2-FA-RGD and the efficacy of the drug carrier PTX@MSNs-NH2-FA-RGD were assessed by cell experiments.Results: The characterization showed successful construction of a dual-targeted mesoporous silica nanocarrier. Obvious differences were detected in the fluorescence intensity of the three cell lines. The results of the pharmacological tests indicated that the blank nanoparticles do not cause any apparent toxicity on these cells. The IC50 of free PTX and PTX@MSNs-NH2-FA-RGD on MCF-7 cells line treated for 48 h were 35.25±2.57 ng·ml-1 and 22.21±3.4 ng·ml-1 respectively, which indicated that the inhibitory efficacy of PTX@MSNs-NH2-FA-RGD on MCF-7 was 1.6 times than that of free PTX.Conclusions: The dual-targeted nanocarrier MSNs-NH2-FA-RGD could target breast cancer cells, and sever as a potential candidate in future of drug development.
研究领域:
药理学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 1
·39-44
·
IF 0
Ze-Yong Li,Jing-Jing Hu,Qi Xu,Si Chen,Hui-Zhen Jia,Yun-Xia Sun,Ren-Xi Zhuo,Xian-Zheng Zhang
In this paper, an intracellular glutathione (GSH) responsive mesoporous silica nanoparticle (MSN-S-S-RGD) was developed as a drug nanocarrier by immobilizing the gatekeeper (RGD containing peptide) onto MSNs using disulfide bonds. The antitumor drug, DOX was loaded onto the porous structure of the MSNs and the DOX@MSN-S-S-RGD system has been proved to be an effective nanocarrier. It was determined that most of the drug could be entrapped with only a slight leakage. After being accumulated in tumor cells via the receptor-mediated endocytosis, the surface peptide layer of DOX@MSN-S-S-RGD was removed to trigger the release of the entrapped drug to kill the tumor cell due to the cleavage of the disulfide bonds by intracellular GSH.
研究领域:
纳米医学
·
肿瘤学
·
生物材料科学
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产品关联
DOI
PubMed
JOURNAL OF CONTROLLED RELEASE
·
2010
·
IF 5.949
Changyou Zhan,Bing Gu,Cao Xie,Jin Li,Yu Liu,Weiyue Lu
The use of glioblastoma-targeted drug delivery system facilitates efficient delivery of chemotherapeutic agents to malignant gliomas in the central nervous system while minimizing high systemic doses associated with debilitating toxicities. To employ the high binding affinity of a cyclic RGD peptide (c(RGDyK), cyclic Arginine–Glycine–Aspartic acid- d -Tyrosine-Lysine) with integrin α v β 3 over-expressed on tumor neovasculature and U87MG glioblastoma cells, we prepared paclitaxel-loaded c(RGDyK)-Poly(ethylene glycol)- block -poly(lactic acid) micelle (c(RGDyK)-PEG-PLA-PTX). In vitro physicochemical characterization of these novel micelles showed satisfactory encapsulated efficiency, loading capacity and size distribution. In vitro cytotoxicity studies proved that the presence of c(RGDyK) enhanced the anti-glioblastoma cell cytotoxic efficacy by 2.5 folds. The binding affinity of c(RGDyK)-PEG-PLA micelle with U87MG cells was also investigated. The competitive binding IC 50 value of c(RGDyK)-PEG-PLA micelle was 26.30 nM, even lower than that of c(RGDyK) (56.23 nM). In U87MG glioblastoma-bearing nude mice model, biodistribution of 125 I-radiolabeled c(RGDyK)-PEG-PLA or DiR encapsulated micelles and anti-glioblastoma pharmacological effect was investigated after intravenous administration. c(RGDyK)-PEG-PLA micelle accumulated in the subcutaneous and intracranial tumor tissue, and when loaded with PTX (c(RGDyK)-PEG-PLA-PTX), exhibited the strongest tumor growth inhibition among the studied paclitaxel formulations. The anti-glioblastoma effect of c(RGDyK)-PEG-PLA-PTX micelle was also reflected in the median survival time of mice bearing intracranial U87MG tumor xenografts where the median survival time of c(RGDyK)-PEG-PLA-PTX micelle-treated mice (48 days) was significantly longer than that of mice treated with PEG-PLA-PTX micelle (41.5 days), Taxol® (38.5 days) or saline (34 days). Therefore, our results suggested that c(RGDyK)-PEG-PLA micelle may be a potential drug delivery system in the treatment of integrin α v β 3 over-expressed glioblastoma.
研究领域:
药学
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肿瘤学
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神经科学
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DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2025
·Vol. 36
·期 30
·305101
·
IF 2.8
Gaojian Liu,Wenjing Wen,Xuan Zhao,Yanan Jing,Hao Li,Xulong Fan,ZiXuan Huang,Gaofeng Liang
Breast cancer is the most prevalent fatal cancer among women worldwide and the leading cause of death for women. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, triggered by the inhibition of the cellular antioxidant system. Photodynamic therapy (PDT) employs photosensitizers to produce reactive oxygen species (ROS), increasing oxidative stress in tumor cells. When combined with ferroptosis, PDT can work synergistically to regulate intracellular redox balance. In this study, we designed engineered nano-erythrocyte membranes for targeted delivery of Chlorin e6 (Ce6) and cisplatin (DDP) to enhance breast cancer treatment. By using mild ultrasound, Ce6 and DDP were co-loaded onto the nano-erythrocyte membranes, combining ferroptosis inducers and photosensitizers to combat breast cancer. To improve targeting capability towards breast cancer, RGD cyclic peptides were modified onto the nano-erythrocyte membranes through a thiol–maleimide coupling reaction. The RGD-modified nano-erythrocyte membranes co-loaded with Ce6 and DDP not only inherited the good stability and significant biocompatibility of red blood cell membranes but also promoted the uptake by breast cancer cells, effectively inducing ferroptosis in these cells. In conclusion, this multifunctional ‘natural’ nanodrug delivery system provides an effective and safe method for PDT combined with ferroptosis for breast cancer treatment.
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2015
·Vol. 183
·期 2
·683-688
·
IF 3.741
Jia Shengsong,Li Pengfei,Koh Kwangnak,Chen Hongxia
The article describes the use of a designed histidine (His)-tagged arginine-glycine-aspartic acid (RGD) peptide as a linker to bind integrin to captured cancer cells, and how to amplify the surface plasmon resonance (SPR) signal after binding of NiO nanoparticles (NiO-NPs) via the His-tag on the peptide. Specifically, breast cancer cells were captured via the interaction between human mucin (MUC-1) and a gold surface modified with a MUC-selective aptamer. The resulting cytosensor exhibits specificity and high sensitivity which is due to the enhancement of the SPR signal by NiO-NPs. The breast cancer cell line MCF-7 can be easily distinguished from normal islet beta cells by using this biosensor. Implementation of the His-tagged RGD peptide modified with NiO-NPs resulted in 20-fold enhancement of the SPR signal at the limit of detection. Hence, the actual limit of detection is lowered to 136 cells per mL. In our perception, this cytosensor has a large clinical potential in that it may also be used to detect various other kinds of tumor cells.
Histidine-tagged arginine-glycine-aspartic acid peptide carried by NiO interacts with the integrin of cancer cells and amplifies the SPR signal resulting from interaction between human mucin (MUC-1) and a gold surface modified with a MUC-selective aptamer. As little as 136 cells·mL −1 are detectable.
研究领域:
生物传感技术
·
肿瘤检测
·
医学诊断
✓ 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）