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      The role of PEG conformation in mixed layers: from protein corona substrate to steric stabilization avoiding protein adsorption

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          Abstract

          Although nanoparticles (NPs) have been traditionally modified with a single ligand layer, mixture of ligands might help to combine different functionalities and to further engineer the NP surface. A detailed study of the competition between an alkanethiol (11-mercaptoundecanoic acid) and SH-PEG for the surface of AuNPs and the resultant behaviors of this model nanoconjugate is presented here. As a result, the physicochemical properties of these conjugates can be progressively tuned by controlling the composition and especially the conformation of the mixed monolayer. This has implications in the physiological stability. The controlled changes on the SH-PEG conformation rather than its concentration induce a change in the stabilization mechanism from electrostatic repulsion to steric hindrance, which changes the biological fate of NPs. Importantly, the adsorption of proteins on the conjugates can be tailored by tuning the composition and conformation of the mixed layer.

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          Most cited references 35

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          Mediating tumor targeting efficiency of nanoparticles through design.

          Here we systematically examined the effect of nanoparticle size (10-100 nm) and surface chemistry (i.e., poly(ethylene glycol)) on passive targeting of tumors in vivo. We found that the physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their tumor accumulation capacity. Interestingly, the permeation of nanoparticles within the tumor is highly dependent on the overall size of the nanoparticle, where larger nanoparticles appear to stay near the vasculature while smaller nanoparticles rapidly diffuse throughout the tumor matrix. Our results provide design parameters for engineering nanoparticles for optimized tumor targeting of contrast agents and therapeutics.
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            Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique.

            The need to characterize nanoparticles in solution before assessing the in vitro toxicity is a high priority. Particle size, size distribution, particle morphology, particle composition, surface area, surface chemistry, and particle reactivity in solution are important factors which need to be defined to accurately assess nanoparticle toxicity. Currently, there are no well-defined techniques for characterization of wet nanomaterials in aqueous or biological solutions. Previously reported nanoparticle characterization techniques in aqueous or biological solutions have consisted of the use of ultra-high illumination light microscopy and disc centrifuge sedimentation; however, these techniques are limited by the measurement size range. The current study focuses on characterizing a wide range of nanomaterials using dynamic light scattering (DLS) and transmission electron microscopy, including metals, metal oxides, and carbon-based materials, in water and cell culture media, with and without serum. Cell viability and cell morphology studies were conducted in conjunction with DLS experiments to evaluate toxicological effects from observed agglomeration changes in the presence or absence of serum in cell culture media. Observations of material-specific surface properties were also recorded. It was also necessary to characterize the impact of sonication, which is implemented to aid in particle dispersion and solution mixture. Additionally, a stock solution of nanomaterials used for toxicology studies was analyzed for changes in agglomeration and zeta potential of the material over time. In summary, our results demonstrate that many metal and metal oxide nanomaterials agglomerate in solution and that depending upon the solution particle agglomeration is either agitated or mitigated. Corresponding toxicity data revealed that the addition of serum to cell culture media can, in some cases, have a significant effect on particle toxicity possibly due to changes in agglomeration or surface chemistry. It was also observed that sonication slightly reduces agglomeration and has minimal effect on particle surface charge. Finally, the stock solution experienced significant changes in particle agglomeration and surface charge over time.
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              Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection.

              Besides toxicity tests, biokinetic studies are a fundamental part of investigations to evaluate a safe and sustainable use of nanoparticles. Today, gold nanoparticles (Au NPs) are known to be a versatile tool in different areas such as science, engineering or medicine. In this study, we investigated the biokinetics after intravenous and intratracheal applications of poly(ethylene glycol) (PEG) modified Au NPs compared to plain Au NPs. Radioactive-labeled Au NPs of 5 nm inorganic core diameter were applied to rats and the NP content in tissues, organs and excretion were quantified after 1-hour and 24-hours. After intravenous injection, a prolonged blood circulation time was determined for Au NPs with 10 kDa PEG chains. Non-PEGylated Au NPs and 750 Da PEG Au NPs accumulated mostly in liver and spleen. After intratracheal application the majority of all three types of applied NPs stayed in the lungs: the total translocation towards the circulation did not differ considerably after PEGylation of the Au NPs. However, a prolonged retention time in the circulation was detected for the small fraction of translocated 10 kDa PEG Au NPs, too. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                SOR-MATSCI
                ScienceOpen Research
                ScienceOpen
                2199-1006
                23 March 2015
                : 0 (ID: fc4bce98-862b-415a-9f28-d891d214535c )
                : 0
                : 1-10
                Affiliations
                [1 ]Insitut Català de Nanociència i Nanotecnologia, Campus UAB, 08193 Barcelona, Spain
                [2 ]Institut Català de Recerca i Estudis Avançats, 08010 Barcelona, Spain
                [3 ]Vall d Hebron Research Insitute, 08035 Barcelona, Spain
                Author notes
                [* ]Corresponding author's e-mail address: victor.puntes@ 123456icn.cat

                Present address: Joan Comenge, Institute of Integrative Biology, University of Liverpool, L69 7ZB Liverpool, UK

                Article
                2676:XE
                10.14293/S2199-1006.1.SOR-MATSCI.A0Z6OM.v1
                © 2015 J. Come and V.F. Puntes.

                This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

                Page count
                Figures: 6, Tables: 0, References: 48, Pages: 10
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