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Behzad Adibi-Motlagh, Abbas Sahebghadam Lotfi, Aram Rezaei, Ehsan Hashemi
The immobilization of bioactive peptides as key molecules in numerous biological and physiological functions holds promise for designing advanced biomaterials. Graphene and its derivatives, having unique physicochemical properties, have brought considerable attention in the life sciences. In this regard, the chemical manipulation of the graphene surface with bioactive peptides opens a new horizon to design bioactive materials for a variety of future nanobiotechnologies. In this study, the first straightforward strategy for the covalent immobilization of the cell-adhesion peptide onto the graphene surface based on the Ugi four-component assembly process (Ugi 4-CAP) will be presented...
January 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Won Jai Lee, Hyo Min Ahn, Youjin Na, Renu Wadhwa, JinWoo Hong, Chae-Ok Yun
Mortalin (Mot) is a mitochondrial chaperone of the heat shock protein 70 family and it's pro-proliferative and anti-apoptosis functions could be associated with keloid pathogenesis, and blocking of mortalin and its interaction with p53 might be a potential novel target for the treatment of keloid. Therefore, we generated mortalin-specific small hairpin (sh) RNAs (dE1-RGD/GFP/shMot) and introduced into keloid spheroids for examination of its apoptotic and anti-fibrotic effect. On keloid tissues, mortalin expression was higher than adjacent normal tissues and it's protein expressions were activated keloid fibroblasts (KFs)...
October 11, 2017: Scientific Reports
Lindy K Jang, Semin Kim, Jiwon Seo, Jae Young Lee
Electrically conductive polymers, such as polypyrrole (PPy), have been widely used for the fabrication of various biosensors and tissue engineering scaffolds. For their biologically relevant applications, conductive biomaterials capable of intimate cellular interactions are highly desired. However, conventional methods to incorporate biomolecules into conductive polymers do not offer fine and easy control over the surface density of the biomolecules and/or their stability. We present a novel method to electrochemically immobilize cell adhesive Arg-Gly-Asp (RGD) ligands on PPy electrode surfaces with a simple control over the peptide surface density by varying the electrodeposition time...
October 11, 2017: Biofabrication
Keren Cohen, Uri Abadi, Aleck Hercbergs, Paul J Davis, Martin Ellis, Osnat Ashur-Fabian
Multiple myeloma (MM) is a plasma cell malignancy in which involvement of the thyroid hormone-integrin αvβ3 pathway was shown and pharmacologic inhibition of this pathway is a rational approach to disease management. A thyroid hormone derivative, tetraiodothyroacetic acid (tetrac), which inhibits L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) binding to αvβ3 integrin, was studied in five MM cell lines and primary bone marrow (BM) MM cells. Tetrac inhibited MM cell proliferation (absolute cell number/viability) and induced caspase-dependent apoptosis (annexin-V/PI and cell cycle)...
October 10, 2017: Endocrine-related Cancer
Yuqian Zhang, Weijun Xiu, Yiting Sun, Di Zhu, Qi Zhang, Lihui Yuwen, Lixing Weng, Zhaogang Teng, Lianhui Wang
The fast-developing field of nanotechnology provides unprecedented opportunities for the increasing demands of biomedicine, especially for cancer diagnostics and treatment. Here, novel multifunctional zero-dimensional-two-dimensional (0D-2D) RGD-QD-MoS2 nanosheets (NSs) with excellent fluorescence, photothermal conversion, and cancer-targeting properties were successfully prepared by functionalizing single-layer MoS2 NSs with fluorescent quantum dots (QDs) and arginine-glycine-aspartic (RGD) containing peptides...
October 10, 2017: Nanoscale
Jie Wang, Wei Li, Zhichao Lu, Leicheng Zhang, Yu Hu, Qiubai Li, Wei Du, Xiaojun Feng, Haibo Jia, Bi-Feng Liu
Promoted therapeutic angiogenesis is a major objective in the area of regenerative medicine, and sufficient vascularization of artificial tissues or organs is one of the main difficulties for the realization of tissue engineering methods. The identification of new kinds of pro-angiogenic materials will greatly profit developments in regenerative medicine. The use of exosomes for this intention is a considerably new idea developed in recent years. However, several limitations need to be addressed before their use as clinical therapeutics, including the lack of efficient exosome enrichment and methods to endow exosomes with targeting ability...
October 9, 2017: Nanoscale
Dimple Chouhan, G Janani, Bijayashree Chakraborty, Samit K Nandi, Biman B Mandal
Chronic cutaneous ulcers, a complex pathophysiological diabetic condition, represent a critical clinical challenge in the current diabetes mellitus pandemic. Consequently, there is a compelling need for bioactive dressings which can trigger healing processes for complete wound repair. Silk fibroin (SF), a natural protein polymer from mulberry and non-mulberry silkworms, has properties that support accelerated wound healing rate. SF from non-mulberry variety possesses additional cell-binding motifs (RGD), offering cell-material interactions...
October 7, 2017: Journal of Tissue Engineering and Regenerative Medicine
Nikolce Gjorevski, Matthias P Lutolf
Growing cells within an extracellular matrix-like 3D gel is required for, or can improve, the growth of many cell types ex vivo. Here, we describe a protocol for the generation of well-defined matrices for the culture of intestinal stem cells (ISCs) and intestinal organoids. These matrices comprise a poly(ethylene glycol) (PEG) hydrogel backbone functionalized with minimal adhesion cues including RGD (Arg-Gly-Asp), which is sufficient for ISC expansion, and laminin-111, which is required for organoid formation...
November 2017: Nature Protocols
Weishan Chang, Yusuke Koba, Tetsurou Katayose, Keisuke Yasui, Chihiro Omachi, Masatsugu Hariu, Hidetoshi Saitoh
To measure the absorbed dose to water <i>D</i><sub>w</sub> in proton beams by radiophotoluminescent glass dosimeter (RGD), a method with the correction for the change of the mass stopping power ratio (SPR) and the linear energy transfer (LET) dependence of radiophotoluminescent (RPL) efficiency ε<sup>RGD</sup><sub>LET</sub> has been proposed. The calibration coefficient in terms of <i>D</i><sub>w</sub> for RGDs (GD-302M, Asahi Techno Glass) was obtained using a <sup>60</sup>Co γ-ray...
October 5, 2017: Physics in Medicine and Biology
Zakia Belhadj, Changyou Zhan, Man Ying, Xiaoli Wei, Cao Xie, Zhiqiang Yan, Weiyue Lu
Glioblastoma multiforme (GBM) has been considered to be the most malignant brain tumors. Due to the existence of various barriers including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) greatly hinder the accumulation and deep penetration of chemotherapeutics, the treatment of glioma remains to be the most challenging task in clinic. In order to circumvent these hurdles, we developed a multifunctional liposomal glioma-targeted drug delivery system (c(RGDyK)/pHA-LS) modified with cyclic RGD (c(RGDyK)) and p-hydroxybenzoic acid (pHA) in which c(RGDyK) could target integrin αvβ3 overexpressed on the BBTB and glioma cells and pHA could target dopamine receptors on the BBB...
September 15, 2017: Oncotarget
Fenfen Zheng, Penghui Zhang, Yu Xi, Xueqin Chen, Zhimei He, Tiantian Meng, Jingjia Chen, Lingling Li, Jun-Jie Zhu
Precisely controlled drug release is a great challenge in exploring methodology of drug administration and fighting drug resistance for successful cancer chemtherapy. Herein, we developed a dual-mode nanocarrier to specifically deliver doxorubicin (Dox) and precisely control the drug release in target tumor cells. This hierarchical nanocarrier consisted of gold nanorod as heating core, biodegradable mesoporous silica as storage chamber, and graphene quantum dot (GQD) as drug carrier. The RGD peptides on nanocarrier surface facilitated the specific interaction with integrin-overexpressed tumor cells and subsequent uptake via receptor-mediated endocytosis...
October 4, 2017: ACS Applied Materials & Interfaces
Kazuki Fukushima, Yuto Inoue, Yuta Haga, Takayuki Ota, Kota Honda, Chikako Sato, Masaru Tanaka
We developed a biodegradable polycarbonate that demonstrates antithrombogenicity and vascular cell adhesion via organocatalytic ring-opening polymerization of a trimethylene carbonate (TMC) analog bearing a methoxy group. The monoether-tagged polycarbonate demonstrates a platelet adhesion property, 93% and 89% lower than poly(ethylene terephthalate) and polyTMC, respectively. In contrast, vascular cell adhesion properties of the polycarbonate are comparable to those controls, indicating a potential for selective cell adhesion properties...
October 3, 2017: Biomacromolecules
M Heller, V V Kumar, A Pabst, J Brieger, B Al-Nawas, P W Kämmerer
Biomimetic surface modifications of titanium implants using the Arg-Gly-Asp-sequence (RGD) are promising to accelerate bone healing in cases of medical implants. Therefore, we compared the impact of linear and cyclic RGD (l- and c-RGD) covalently coupled onto titanium surfaces on the osseous response in vitro and in vivo. In vitro, osteoblasts' behaviour on different surfaces (unmodified, amino-silanized (APTES), l- and c-RGD) was analysed regarding adhesion (fluorescence microscopy), proliferation (resazurin stain) and differentiation (RT-PCR on alkaline phosphatase (AP) & osteocalcin (OC))...
October 3, 2017: Journal of Biomedical Materials Research. Part A
Yongjing Li, Jiaxun Wan, Zihao Zhang, Jia Guo, Changchun Wang
The development of multifunctional ultrasound contrast agents has inspired considerable interest in the application of biomedical imaging and anticancer therapeutics. However, combining multiple components that can preferentially accumulate in tumors in a nanometer scale poses one of the major challenges in targeting drug delivery for theranostic application. Herein, reflux-precipitation polymerization, and N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide-meditated amidation reaction were introduced to effectively generate a new type of soft glycine/poly(ethylene glycol) (PEG)/RGD-modified poly(methacrylic acid) nanobubbles with a uniform morphology and desired particle size (less than 100 nm)...
October 9, 2017: ACS Applied Materials & Interfaces
Guoqing Pan, Sudhirkumar Shinde, Sing Yee Yeung, Miglė Jakštaitė, Qianjin Li, Anette Gjörloff Wingren, Börje Sellergren
In this work, an epitope imprinting strategy was successfully employed to dynamically display bioactive ligands on the material interface. An imprinted surface was initially designed to exhibit specific affinity towards a short peptide (i.e., the epitope). This surface was subsequently used to anchor an epitope-tagged cell adhesive peptide ligand (RGD: Arg-Gly-Asp). Owing to reversible epitope binding affinity, both ligand presentation and thereby cell adhesion could be controlled. Compared to current strategies for fabrication of dynamic biointerfaces, e...
September 28, 2017: Angewandte Chemie
Massimo Serra, Elena Giulia Peviani, Eric Bernardi, Lino Colombo
7,5-Fused azabicycloalkane scaffolds, carrying a quaternary stereocenter at C3 position of the lactam ring, can act as effective reverse-turn mimics and have proven to be useful intermediates for the preparation of Arg-Gly-Asp (RGD)-based cyclopentapeptides (cRGD) with nanomolar activity as αvβ3/αvβ5 integrin antagonists. Here, we report the synthesis of new azabicycloalkane scaffolds endowed at the C6 position with a para-substituted phenethyl side chain, which could be exploited to obtain cRGD-based bioconjugates that may find promising applications in anticancer therapy...
October 4, 2017: Journal of Organic Chemistry
Richard Hatley, Simon Macdonald, Robert Slack, Joelle Le, Steve Ludbrook, Pauline Lukey
There is a requirement for efficacious and safe medicines to treat diseases with high unmet need. The resurgence in av RGD integrin inhibitor drug discovery is poised to contribute to this requirement. However, drug discovery in the av integrin space is notoriously difficult due to the receptors being structurally very similar as well as the polar zwitterionic nature of the pharmacophore. This review aims to guide drug discovery research in this field through an av inhibitor toolbox, consisting of small molecules and antibodies...
September 25, 2017: Angewandte Chemie
Jugal P Dhandhukia, Pu Shi, Santosh Peddi, Zhe Li, Suhaas Rayudu Aluri, Yaping Ju, Dab Brill, Wan Wang, Siti Janib, Yi-An Lin, Shuanglong Liu, Honggang Cui, John Andrew MacKay
Recombinant protein-polymer scaffolds such as Elastin-Like Polypeptides (ELPs) offer drug delivery opportunities including biocompatibility, monodispersity, and multi-functionality. We recently reported that fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses growth of breast cancer xenografts, and reduces side-effects observed with free drug controls. This new report significantly advances this carrier strategy by demonstrating the co-assembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains...
September 22, 2017: Bioconjugate Chemistry
Monica Civera, Daniela Arosio, Francesca Bonato, Leonardo Manzoni, Luca Pignataro, Simone Zanella, Cesare Gennari, Umberto Piarulli, Laura Belvisi
The interaction of a small library of cyclic RGD (Arg-Gly-Asp) peptidomimetics with αVβ₆ integrin has been investigated by means of competitive solid phase binding assays to the isolated receptor and docking calculations in the crystal structure of the αVβ₆ binding site. To this aim, a rigid receptor-flexible ligand docking protocol has been set up and then applied to predict the binding mode of the cyclic RGD peptidomimetics to αVβ₆ integrin. Although the RGD interaction with αVβ₆ recapitulates the RGD binding mode observed in αVβ₃, differences between the integrin binding pockets can strongly affect the ligand binding ability...
September 21, 2017: Cancers
Paolo Durigutto, Daniele Sblattero, Stefania Biffi, Luca De Maso, Chiara Garrovo, Gabriele Baj, Federico Colombo, Fabio Fischetti, Antonio F Di Naro, Francesco Tedesco, Paolo Macor
Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process...
2017: Frontiers in Immunology
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