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https://www.readbyqxmd.com/read/28643235/design-and-evaluation-of-rgd-modified-gemini-surfactant-based-lipoplexes-for-targeted-gene-therapy-in-melanoma-model
#1
Waleed Mohammed-Saeid, Jackson Chitanda, Mays Al-Dulaymi, Ronald Verrall, Ildiko Badea
PURPOSE: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. METHODS: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed. Transfection efficiency and cellular toxicity of the lipoplexes were evaluated in an in vitro human melanoma model...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28637399/biomineralized-recombinant-collagen-based-scaffold-mimicking-native-bone-enhances-mesenchymal-stem-cell-interaction-and-differentiation
#2
Gloria Belén Ramirez-Rodríguez, Monica Montesi, Silvia Panseri, Simone Sprio, Anna Tampieri, Monica Sandri
The need of synthetic bone grafts that recreate from macro to nanoscale level the biochemical and biophysical cues of bone extracellular matrix (ECM) has been a major driving force for the development of new generation of biomaterials. In this study, synthetic bone substitutes have been synthesized via biomimetic mineralization of a recombinant collagen type I derived peptide (RCP), enriched in tri-amino acid sequence arginine-glycine-aspartate (RGD). 3D isotropic porous scaffolds of three different compositions are developed by freeze-drying: non-mineralized (RCP, as a control), mineralized (Ap/RCP) and mineralized scaffolds in presence of magnesium (MgAp/RCP) that closely imitate bone composition...
June 22, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28632139/peptide-functionalized-gold-nanoparticles-the-influence-of-ph-on-binding-efficiency
#3
Emma Harrison, Jeremy Hamilton, Manuel Montero, Dorian Dixon
We report herein on the synthesis of mixed monolayer gold nanoparticles (AuNPs) capped with both polyethylene glycol (PEG) and one of three peptides. Either a receptor-mediated endocytosis (RME) peptide, an endosomal escape pathway (H5WYG) peptide or the Nrp-1 targeting RGD peptide (CRGDK) labelled with FITC. All three peptides have a thiol containing cysteine residue which can be used to bind the peptides to the AuNPs. In order to investigate the influence of pH on peptide attachment, PEGylated AuNPs were centrifuged, the supernatant removed, and the nanoparticles were then re-suspended in a range of pH buffer solutions above, below and at the respective isoelectric points of the peptides before co-functionalization...
June 20, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28629432/imaging-of-%C3%AE-v%C3%AE-3-integrin-expression-in-experimental-myocardial-ischemia-with-68-ga-nodaga-rgd-positron-emission-tomography
#4
Maria Grönman, Miikka Tarkia, Tuomas Kiviniemi, Paavo Halonen, Antti Kuivanen, Timo Savunen, Tuula Tolvanen, Jarmo Teuho, Meeri Käkelä, Olli Metsälä, Mikko Pietilä, Pekka Saukko, Seppo Ylä-Herttuala, Juhani Knuuti, Anne Roivainen, Antti Saraste
BACKGROUND: Radiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [(68)Ga]NODAGA-RGD detects increased αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ3 integrin is expressed in viable ischemic or injured myocardium. METHODS: We studied 8 Finnish landrace pigs 13 ± 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery...
June 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28626568/dual-targeted-peptide-conjugated-multifunctional-fluorescent-probe-with-aiegen-for-efficient-nucleus-specific-imaging-and-long-term-tracing-of-cancer-cells
#5
Yong Cheng, Chunli Sun, Xiaowen Ou, Bifeng Liu, Xiaoding Lou, Fan Xia
Precisely targeted transportation of a long-term tracing regent to a nucleus with low toxicity is one of the most challenging concerns in revealing cancer cell behaviors. Here, we report a dual-targeted peptide-conjugated multifunctional fluorescent probe (cNGR-CPP-NLS-RGD-PyTPE, TCNTP) with aggregation-induced emission (AIE) characteristic, for efficient nucleus-specific imaging and long-term and low-toxicity tracing of cancer cells. TCNTP mainly consists of two components: one is a functionalized combinatorial peptide (TCNT) containing two targeted peptides (cNGR and RGD), a cell-penetrating peptide (CPP) and a nuclear localization signal (NLS), which can specifically bind to a cell surface and effectively enter into the nucleus; the other one is an AIE-active tetraphenylethene derivative (PyTPE, a typical AIEgen) as fluorescence imaging reagent...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28620939/engineering-novel-targeted-boron-10-enriched-theranostic-nanomedicine-to-combat-against-murine-brain-tumors-via-mr-imaging-guided-boron-neutron-capture-therapy
#6
Naresh Kuthala, Raviraj Vankayala, Yi-Nan Li, Chi-Shiun Chiang, Kuo Chu Hwang
Glioblastoma multiforme (GBM) is a very common type of "incurable" malignant brain tumor. Although many treatment options are currently available, most of them eventually fail due to its recurrence. Boron neutron capture therapy (BNCT) emerges as an alternative noninvasive therapeutic treatment modality. The major challenge in treating GBMs using BNCT is to achieve selective imaging, targeting, and sufficient accumulation of boron-containing drug at the tumor site so that effective destruction of tumor cells can be achieved without harming the normal brain cells...
June 16, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28617486/ultra-high-loading-of-sinoporphyrin-sodium-in-ferritin-for-single-wave-motivated-photothermal-and-photodynamic-co-therapy
#7
Chao Huang, Chengchao Chu, Xiaoyong Wang, Huirong Lin, Junqing Wang, Yun Zeng, Wenzhen Zhu, Yi-Xiang J Wang, Gang Liu
In this work, a potent photosensitizer, sinoporphyrin sodium (DVDMS), was loaded into RGD-modified ferritin (R-Fn) nanocages by a rapid, scalable and versatile approach for imaging guided photodynamic and photothermal (PTT/PDT) co-therapy. The resulting nanocomposite formed a well-defined nanocage with a photosensitizer loading capacity as high as 66.67 wt%, which far exceeds those reported previously. The bioengineered protein nanocage-based nanotheranostics exhibits a remarkably improved tumor treatment effect over DVDMS with good biocompatibility and the potential of clinical translation...
June 15, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28611426/radioiodination-of-bodipy-and-its-application-to-a-nuclear-and-optical-dual-functional-labeling-agent-for-proteins-and-peptides
#8
Masahiro Ono, Hiroyuki Watanabe, Yuki Ikehata, Ning Ding, Masashi Yoshimura, Kohei Sano, Hideo Saji
In molecular imaging research, the development of multimodal imaging probes has recently attracted much attention. In the present study, we prepared radioiodinated BODIPY and applied it as a nuclear and optical dual functional labeling agent for proteins and peptides. We designed and synthesized [(125)I]BODIPY with a N-hydroxysuccinimide (NHS) ester, and evaluated its utility as a nuclear and fluorescent dual labeling agent for proteins and peptides. In the radioiodination reaction of BODIPY-NHS with [(125)I]NaI, [(125)I]BODIPY-NHS was obtained at a 48% radiochemical yield...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28608961/high-affinity-click-rgd-peptidomimetics-as-radiolabeled-probes-for-imaging-%C3%AE-v%C3%AE-3-integrin
#9
Monica Piras, Andrea Testa, Ian N Fleming, Sergio Dall'Angelo, Alexandra Andriu, Sergio Menta, Mattia Mori, Gavin D Brown, Duncan Forster, Kaye J Williams, Matteo Zanda
Non-peptidic RGD-mimic ligands were designed and synthesized by click chemistry between an arginine-azide mimic and an aspartic acid-alkyne mimic. Some of these molecules combine excellent in vitro properties (high αvβ3 affinity, selectivity, drug-like logD, high metabolic stability) with a variety of radiolabeling options (e.g. tritium and [18F]fluorine, plus compatibility with radio-iodination), not requiring the use of chelators or prosthetic groups. The binding mode of the resulting triazole RGD-mimics to αvβ3 or αIIbβ3 receptors was investigated by molecular modeling simulations...
June 13, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28606509/targeting-integrin-rich-tumors-with-temoporfin-loaded-vitamin-e-succinate-grafted-chitosan-oligosaccharide-d-%C3%AE-tocopheryl-polyethylene-glycol-1000-succinate-nanoparticles-to-enhance-photodynamic-therapy-efficiency
#10
Junru Wu, Shu Feng, Wenchao Liu, Feng Gao, Yanzuo Chen
A major challenge in cancer photodynamic therapy (PDT) is the poor tumor selectivity of the photosensitizer. Therefore, temoporfin (mTHPC)-loaded nanoparticles, based on vitamin-E-succinate-grafted chitosan oligosaccharide and cyclic (arginine-glycine-aspartic acid-d-phenylalanine-lysine) (c[RGDfK])-modified d-α-tocopheryl polyethylene glycol 1000 succinate, were prepared (RGD-NPs) and were expected to enhance the accumulation of mTHPC in integrin-rich U87MG tumors. The RGD-NPs generated were 144.9nm in diameter and uniformly spherical...
June 9, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28606226/-expression-of-%C3%AE-integrin-family-members-in-children-with-t-cell-acute-lymphoblastic-leukemia
#11
Qing-Lin Kong, Xi-Zhou An, Xian-Min Guan, Yi-Mei Ma, Peng-Fei Li, Shao-Yan Liang, Yan-Ni Hu, Ying-Hui Cui, Jie Yu
OBJECTIVE: To study the expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance. METHODS: Quantitative real-time PCR analyses were performed to assess the expression levels of β-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28602859/fibroblast-fibronectin-patterning-and-network-formation-in-3d-fibrin-matrices
#12
Miguel Miron-Mendoza, Eric Graham, Sujal Manohar, W Matthew Petroll
PURPOSE: We previously reported that fibroblasts migrating within 3-D collagen matrices move independently, whereas fibroblasts within 3-D fibrin matrices form an interconnected network. Similar networks have been identified previously during in vivo corneal wound healing. In this study, we investigate the role of fibronectin in mediating this mechanism of collective cell spreading, migration and patterning. METHODS: To assess cell spreading, corneal fibroblasts were plated within fibrillar collagen or fibrin matrices...
June 7, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28600529/synthesis-chemical-characterization-and-multiscale-biological-evaluation-of-a-dimeric-crgd-peptide-for-targeted-imaging-of-%C3%AE-v-%C3%AE-3-integrin-activity
#13
Jamila Hedhli, Andrzej Czerwinski, Matthew Schuelke, Agata Płoska, Paweł Sowinski, Lukas La Hood, Spencer B Mamer, John A Cole, Paulina Czaplewska, Maciej Banach, Iwona T Dobrucki, Leszek Kalinowski, Princess Imoukhuede, Lawrence W Dobrucki
Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α V β 3 integrin. We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of α V β 3 activity (a radiolabeled version, (64)Cu-NOTA-PEG4-cRGD2, for PET imaging, and a fluorescent version, FITC-PEG4-cRGD2, for in vitro work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28594999/regenerating-bone-via-multifunctional-coatings-the-blending-of-cell-integration-and-bacterial-inhibition-properties-on-the-surface-of-biomaterials
#14
Mireia Hoyos-Nogués, Ferran Velasco, Maria-Pau Ginebra, José María Manero, F Javier Gil, Carlos Mas-Moruno
In dentistry and orthopedics, it is well accepted that implant fixation is a major goal. However, an emerging concern is bacterial infection. Infection of metallic implants can be catastrophic and significantly reduce patient quality of life. Accordingly, in this work, we focus on multifunctional coatings to simultaneously address and mitigate both these problems. We have developed a tailor-made peptide-based chemical platform that integrates the well-known RGD cell adhesive sequence and the lactoferrin-derived LF1-11 antimicrobial peptide...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28592490/functional-analyses-yield-detailed-insight-into-the-mechanism-of-thrombin-inhibition-by-the-antihemostatic-salivary-protein-ce5-from-anopheles-gambiae
#15
Luciano Pirone, Jorge Ripoll-Rozada, Marilisa Leone, Raffaele Ronca, Fabrizio Lombardo, Gabriella Fiorentino, John F Andersen, Pedro José Barbosa Pereira, Bruno Arcà, Emilia Pedone
Saliva of blood-feeding arthropods carries several antihemostatic compounds whose physiological role is to facilitate successful acquisition of blood. The identification of novel natural anticoagulants and the understanding of their mechanism of action may offer opportunities for designing new antithrombotics disrupting blood clotting. We report here an in depth structural and functional analysis of the anophelin family member cE5, a salivary protein from the major African malaria vector Anopheles gambiae that specifically tightly and quickly binds and inhibitss thrombin...
June 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28591726/multifunctional-targeted-liposomal-drug-delivery-for-efficient-glioblastoma-treatment
#16
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...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28587135/rgd-binding-integrins-in-head-and-neck-cancers
#17
REVIEW
Hanadi Talal Ahmedah, Laurence H Patterson, Steven D Shnyder, Helen M Sheldrake
Alterations in integrin expression and function promote tumour growth, invasion, metastasis and neoangiogenesis. Head and neck cancers are highly vascular tumours with a tendency to metastasise. They express a wide range of integrin receptors. Expression of the αv and β1 subunits has been explored relatively extensively and linked to tumour progression and metastasis. Individual receptors αvβ3 and αvβ5 have proved popular targets for diagnostic and therapeutic agents but lesser studied receptors, such as αvβ6, αvβ8, and β1 subfamily members, also show promise...
May 26, 2017: Cancers
https://www.readbyqxmd.com/read/28578297/targeting-and-destroying-tumor-vasculature-with-a-near-infrared-laser-activated-nanobomb-for-efficient-tumor-ablation
#18
Wen Gao, Shuangshuang Li, Zhenhua Liu, Yuhui Sun, Wenhua Cao, Lili Tong, Guanwei Cui, Bo Tang
Attacking the supportive vasculature network of a tumor offers an important new avenue for cancer therapy. Herein, a near-infrared (NIR) laser-activated "nanobomb" was developed as a noninvasive and targeted physical therapeutic strategy to effectively disrupt tumor neovasculature in an accurate and expeditious manner. This "nanobomb" was rationally fabricated via the encapsulation of vinyl azide (VA) into c(RGDfE) peptide-functionalized, hollow copper sulfide (HCuS) nanoparticles. The resulting RGD@HCuS(VA) was selectively internalized into integrin αvβ3-expressing tumor vasculature endothelial cells and dramatically increased the photoacoustic signals from the tumor neovasculature, achieving a maximum signal-to-noise ratio at 4 h post-injection...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28575020/ngr-peptide-drug-conjugates-with-dual-targeting-properties
#19
Kata Nóra Enyedi, Szilárd Tóth, Gergely Szakács, Gábor Mező
Peptides containing the asparagine-glycine-arginine (NGR) motif are recognized by CD13/aminopeptidase N (APN) receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integrins provide tumor-homing, which can be exploited for dual targeted delivery of anticancer drugs. We synthesized small cyclic NGR peptide-daunomycin conjugates using NGR peptides of varying stability (c[KNGRE]-NH2, Ac-c[CNGRC]-NH2 and the thioether bond containing c[CH2-CO-NGRC]-NH2, c[CH2-CO-KNGRC]-NH2)...
2017: PloS One
https://www.readbyqxmd.com/read/28571905/extremely-small-sized-globular-poly-ethylene-glycol-cyclic-rgd-conjugates-targeting-integrin-%C3%AE-v%C3%AE-3-in-tumor-cells
#20
Seong Kyeong Kim, Jae Min Lee, Kyung Taek Oh, Eun Seong Lee
In this study, we report an extremely small-sized globular poly(ethylene glycol) (gPEG) conjugated with cyclic arginine-glycine-aspartic acid (cRGD) peptide and chlorin e6 (Ce6). This nanoparticle design takes advantage of the biocompatible functional gPEG (3-4nm in diameter) as an extremely small-sized drug carrier, the tumor targeting ability of cRGD, and the photodynamic tumor ablation ability of Ce6. We found that gPEG conjugated with cRGD and Ce6 (cRGD-gPEG-Ce6) exhibited much higher phototoxicity in SKOV-3 tumor cells (which have a very high density of integrin αvβ3 receptors) than in KB cells (which have a very low density of integrin αvβ3 receptors)...
May 30, 2017: International Journal of Pharmaceutics
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