Peptide Science
·
2022
·Vol. 115
·期 2
·e24302
·
IF 2.592
Anqi Wang,Kai Yue,Yiang Wei,Weishen Zhong,Genpei Zhang
The structural change of receptor protein at high temperatures is one of the factors affecting the targeting ability of ligand-installed nanocarriers for combined therapy of hyperthermia and drug delivery. In this study, the binding behaviors and mechanisms of integrin αvβ3 receptor and the arginine-glycine-aspartic acid (RGD) peptide ligand at high temperatures were investigated both theoretically and experimentally. The structural parameters of integrin αvβ3 at different temperatures and the interaction forces between the RGD peptide and integrin αvβ3 at different binding sites were calculated by molecular dynamics simulation. Fourier transform infrared spectroscopy, energy dispersive spectroscopy, ultraviolet–visible absorption spectroscopy, and atomic force microscopy were used to analyze the structural changes of integrin αvβ3 and to measure the ligand-receptor interaction. Results show that the number of hydrogen bonds decreased and the secondary structure of integrin αvβ3 changed with the increase in temperature, indicating the denaturation of integrin αvβ3. The structural stability of the integrin αv subunit was better than that of the integrin β3 subunit at high temperatures. The interaction between the RGD peptide and integrin αvβ3 weakened as the temperature increased because the structure of the integrin αvβ3 binding site became more flexible and the corresponding calcium ions were shed from the binding site. The strongest interaction force was exhibited at the binding site of the integrin β3 subunit at 310 K while it was found at the binding site of the integrin αv subunit at higher temperatures, owing to the smaller structure deformation of the integrin αv subunit. Graphical
研究领域:
生物物理学
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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
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2018
·
IF 1.883
Jie Liao,Xiaoting Ren,Bowen Yang,Hou Li,Yuexin Zhang,Zongning Yin
Lumbrokinase (LK) has strong fibrinolytic and thrombolytic activities, but it has a short half-life, can be easily inactivated, and may cause hemorrhage as a side effect. This study develops a potential thrombolytic therapy by fabricating N,N,N-Trimethyl Chitosan (TMC) nanoparticles modified with the cyclic Arg-Gly-Asp-Phe-Lys peptide (c-RGD) and loaded with LK (i.e. c-RGD-LK-NPs). The binding of c-RGD to platelet membrane GPIIb/IIIa receptors is expected to enable targeted delivery of the c-RGD-conjugated TMC to the thrombus. The synthesized c-RGD-LK-NPs had a mean particle size of 232.0 nm, zeta potential of 19.8 mV, entrapment efficiency of 52.7% ± 2.5%, and loading efficiency of 17.4% ± 0.65%. Transmission electron microscopy showed that they were generally spherical. The c-RGD-LK-NPs gave a cumulative in vitro LK release of 80.6% over 8 h, and the activity of LK was close to 80%, indicating that the nanoparticles protected the activity of LK. In vitro blood clot lysis assays were carried out and in vivo thrombolysis effect was tested in Sprague-Dawley rats carotid artery thrombus model. In all cases, the c-RGD-LK-NPs showed superior performance compared with the free LK and the unmodified TMC nanoparticles loaded with LK. The c-RGD-LK-NPs reagent is expected to be potentially useful in treating thromboembolic diseases.
研究领域:
药学
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纳米技术
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治疗学
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血液学
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产品关联
DOI
PubMed
高影响因子
Materials
·
2019
·Vol. 12
·期 20
·3391
·
IF 2.972
Zheng Wang,Xiaolu Zhu,Ruiyuan Zhang
The interactions between substrate materials and cells usually play an important role in the hydrogel-based 3D cell cultures. However, the hydrogels that are usually used could not be parametrically regulated, especially for quantitatively regulating the spatial distribution of the adhesion sites for cells in 3D. Here, we employed the semisynthetic hydrogel consisting of maleimide-dextran, Arg-Gly-Asp (RGD) peptides, and cell degradable crosslinkers to biochemically characterize the evolutionary behaviors of NIH–3T3 fibroblasts and C2C12 cells in 3D. Moreover, by comparing the cell-adhesive efficacy of 3D dextran hydrogels with four different RGD clustering rates, we explored the underlying regulation law of C2C12 connections and 3T3 aggregations. The results showed that mal-dextran hydrogel could promise cells stable viability and continuous proliferation, and induce more self-organized multicellular structures relative to 2D culture. More importantly, we found that RGD-clustered mal-dextran hydrogel has the advantage of enhancing C2C12 cell elongation and the breadthwise-aggregated connection, and promoting the 3T3 cell aggregating degree compared to that with homogenous RGD. Further, the advantages of RGD clustering hydrogel could be amplified by appropriately reducing RGD concentration. Such RGD-composition controllable mal-dextran hydrogel can function as a regulator of the collective cellular behaviors, which provides useful information for quantitatively designing the tailored hydrogel system and exploiting advanced biomaterials.Keywords:glycan;maleimide-dextran hydrogel;cell–substrate adhesion;3D culture
研究领域:
生物材料
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细胞生物学
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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 SCIENCE-MATERIALS IN MEDICINE
·
2023
·Vol. 34
·期 4
·1-12
·
IF 3.7
Xu Zichen,Huang Jinxia,Zhang Tao,Xu Wenfeng,Liao Xiaoling,Wang Yi,Wang Guixue
In recent years, the fabrication of nano-drug delivery systems for targeted treatment of thrombus has become a research hotspot. In this study, we intend to construct a biomimetic nanomedicine for targeted thrombus treatment. The poly lactic-co-glycolic acid (PLGA) was selected as the nanocarrier material. Then, urokinase and perfluoro-n-pentane (PFP) were co-loaded into PLGA by the double emulsification solvent evaporation method to prepare phase change nanoparticles PPUNPs. Subsequently, the RGD peptide-modified red blood cell membrane (RBCM) was coated on the surface of PPUNPs to prepare a biomimetic nano-drug carrier (RGD-RBCM@PPUNPs). The as-prepared RGD-RBCM@PPUNPs possessed a “core-shell” structure, have good dispersibility, and inherited the membrane protein composition of RBCs. Under ultrasound stimulation, the loaded urokinase could be rapidly released. In vitro cell experiments showed that RGD-RBCM@PPUNPs had good hemocompatibility and cytocompatibility. Due to the coated RGD-RBC membrane, RGD-RBCM@PPUNPs could effectively inhibit the uptake of macrophages. In addition, RGD-RBCM@PPUNPs showed better thrombolytic function in vitro. Overall, the results suggested that this biomimetic nanomedicine provided a promising therapeutic strategy for the targeted therapy of thrombosis. Graphical Abstract
研究领域:
纳米技术
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药学
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生物医学工程
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治疗学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2022
·Vol. 12
·期 28
·18004-18011
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IF 4.036
Lingling Xu,Chuan Zhou,Fan Wang,Huiqin Liu,Guangyuan Dong,Siyi Zhang,Tao Liu
In this study, a drug delivery system was prepared by grafting the targeting molecule arginine-glycine-aspartic acid (RGD) onto hyperbranched polyglycerol (HPG)-modified β-cyclodextrin (β-CD-HPG) for the targeted inhibition of nasopharyngeal carcinoma (NPC) cells. The obtained β-CD-HPG-RGD with a relatively small size and low surface charge delivered docetaxel (Doc) effectively and displayed a targeting effect to human NPC HNE-1 cells, as confirmed by confocal laser scanning microscopy and flow cytometry. The in vitro drug release analysis exhibited the controlled drug release kinetics of the β-CD-HPG-RGD/Doc nanomedicine. β-CD-HPG-RGD/Doc effectively inhibited the proliferation of HNE-1 cells and promoted apoptosis. Moreover, its biocompatibility in vitro and in vivo was assessed. The results indicate that the β-CD-HPG-RGD/Doc nanomedicine has potential application in NPC targeting therapy.
研究领域:
药剂学
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肿瘤学
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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
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 3
·447-453
·
IF 5.047
Sen Ye,Yang Liu,Yi Lu,Yuqin Ji,Lianlian Mei,Mingwen Yang,Xiaoxuan Gong,Qian Gu,Di Li,Fang Yang,Chun-Jian Li
Thrombotic disease is a serious threat to human health. The rapid and accurate detection of thrombosis is still a clinical challenge. To achieve the accurate diagnosis of thrombosis with magnetic resonance imaging (MRI), nanomaterials-based contrast agents have been developed in recent years. In this study, cyclic RGD functionalized liposomes targeted to the activated platelets are developed for thrombosis dual-mode MRI. The cyclic RGD functionalized liposomes (cRGD@MLP-Gd) encapsulated with gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and superparamagnetic iron oxide (SPIO) are prepared, and their thrombus-targeted T1 and T2 MRI potential is evaluated in vitro and in vivo. Results show that cRGD@MLP-Gd could actively bind to the activated platelets and gradually accumulate at the thrombus site with a T1 − T2 contrast enhancement imaging effect in vitro. In in vivo MRI experiments, cRGD@MLP-Gd exhibits a T2 contrast enhancement at 1 h after intravenous administration, followed by a visibly larger T1 contrast enhancement at the thrombus site. This dynamic property showed that cRGD@MLP-Gd could actively bind to thrombus and possessed an enhanced T1 and T2 dual-mode MRI effect in vivo. Our results establish the characterization, feasibility and superiority of cRGD@MLP-Gd for the rapid identification of thrombosis, showing great potential to improve diagnostic accuracy and sensitivity to thrombosis of the MRI technique.
研究领域:
医学影像
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纳米医学
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诊疗学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yaning Ge,Xin Zhu,Zhengxian Zhang,Huanhuan Zhu,Tianqi Wang,Jingru Cui,Huahui Zeng,Xiangxiang Wu,Zhenqiang Zhang
Triptolide (TP) is a promising anti-tumor candidate derived from the herb Tripterygium wilfordii , but its poor water solubility and multi-organ toxicity limit its application. Here, we developed novel nanoparticles (TP-SP@NPs) modified with dextran sulfate and RGD peptide for double-targeted delivery of TP to both tumor cells and pro-tumor macrophages in pancreatic cancer treatment. TP-SP@NPs exhibited suitable particle size (about 98 nm), good stability and controlled release performance. TP-SP@NPs showed high cellular uptake in Pan02 cells and M2 macrophages through α v β 3 integrin-RGD interaction and SR-A-DS interaction, effectively inhibiting tumor growth by triggering apoptosis of these cells. In Pan02 tumor-bearing mice, TP-SP@NPs specifically accumulated at the tumor site and efficiently decreased the number of M2 macrophages, thereby exerting better curative effect on pancreatic cancer and lower systemic toxicity as compared with TP. As a result, TP-SP@NPs had achieved selective anti-tumor effect, good biosafety and great promise in clinical application.
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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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 8
·期 1
·391-404
·
IF 5.251
Guannan Zhang,Xingyu Zhang,Yongqiang Yang,Ruifang Chi,Jing Shi,Ruiqiang Hang,Xiaobo Huang,Xiaohong Yao,Paul K. Chu,Xiangyu Zhang
Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO2)/molybdenum disulfide (MoS2)/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO2/MoS2 NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.
研究领域:
生物材料
·
纳米技术
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生物医学工程
·
骨科
·
牙科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
·
2021
·Vol. 49
·期 3
·847-860
·
IF 9.236
Liu Jing-Jing,Wang Zun,Nie Li-Ming,Zhu Yuan-Yuan,Li Ge,Lin Lin-Ling,Chen Min,Zhang Guo-Jun
Purpose Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. Methods The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. Results The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. Conclusion These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.
研究领域:
医学影像
·
癌症手术
·
纳米技术
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Dongqin Lei,Jing Xin,Fen Qin,Hongyi Lan,Jing Liu,Sijia Wang,Jing Wang,Weihui Zeng,Cuiping Yao
In photodynamic therapy (PDT), reactive oxygen species (ROS) are key products that induce cell death, and increasing amount of ROS is a crucial way to enhance PDT efficacy. However, the generated ROS stimulates the transient receptor potential vanilloid 1 channel (TRPV1), which can be activated in the pain pathway and then exacerbate pain. Herein, we utilized arginine−glycine−aspartate (RGD) peptide-modified liposomes for encapsulation Chlorin e6 (Ce6) and capsazepine (Cz), a receptor antagonist of TRPV1, to prepare drug-loaded liposomes, RLCC. Soluble hyaluronic acid microneedle arrays (MNs), which possess sufficient skin penetration capability and excellent biosafety, was applied for in situ delivery of RLCC. With the aid of RGD peptides, the efficiency of intracellular liposomal uptake and the dispersion of drugs in tumor after delivery by MNs were significantly enhanced, showcasing tremendous potential for improving the PDT efficacy. Besides, through the analysis of sciatic nerve signals in mice during PDT, RLCC demonstrated remarkable effectiveness in alleviating pain by significantly reducing nerve impulses. Hence, RLCC demonstrated outstanding effectiveness in PDT and effectively alleviated the associated pain. Overall, this research highlights the potential of utilizing MNs for the in situ delivery of RLCC, facilitating effective PDT while addressing the issue of pain during the treatment.
研究领域:
药学
·
生物医学工程
·
疼痛管理
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Feng Chen,Yunzhou Ni,Bing Liu,Tongtong Zhou,Chunyang Yu,Yue Su,Xinyuan Zhu,Xiaowei Yu,Yongfeng Zhou
In the present study, we developed a biomimetic injectable hydrogel system based on hyaluronic acid-adipic dihydrazide and the oligopeptide G 4 RGDS-grafted oxidized pectin, in which their hydrazide and aldehyde-derivatives enable covalent hydrazone crosslinking of polysaccharides. The hydrazone crosslinking strategy is simple, while circumventing toxicity, making this injectable system feasible, minimally invasive and easily translatable for regenerative purposes. By varying their weight ratios, the physicochemical properties of the mechanically stable hydrogel system were easily adjustable. Additionally, the preliminary studies demonstrated that chondrocyte behavior was dependent on HA/pectin composition and the presence of integrin binding moieties. Specifically, the incorporation of a certain amount of G 4 RGDS oligopeptide into HA/pectin-based hydrogels could serve as a biologically active microenvironment that supported chondrocyte phenotype and facilitated chondrogenesis. Furthermore, the hydrogel system exhibited acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable multicomponent hydrogel presented here is expected to be useful biomaterial scaffold for cartilage tissue regeneration.
研究领域:
组织工程
·
生物材料科学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）