1,720,975 research outputs found
Antifolate SERS-active nanovectors: quantitative drug nanostructuring and selective cell targeting for effective theranostics
No full textOne of the frontiers of nanomedicine is the rational design of theranostic nanovectors. These are nanosized materials combining diagnostic and therapeutic capabilities, i.e. capable of tracking cancer cells and tissues in complex environments, and of selectively acting against them. We herein report on the preparation and application of antifolate plasmonic nanovectors, made of functionalized gold nanoparticles conjugated with the folic acid competitors aminopterin and methotrexate. Due to the overexpression of folate binding proteins on many types of cancer cells, these nanosystems can be exploited for selective cancer cell targeting. The strong surface enhanced Raman scattering (SERS) signature of these nanovectors acts as a diagnostic tool, not only for tracing their presence in biological samples, but also, through a careful spectral analysis, to precisely quantify the amount of drug loaded on a single nanoparticle, and therefore delivered to the cells. Meanwhile, the therapeutic action is implemented based on the strong toxicity of antifolate drugs. Remarkably, supplying the drug in the nanostructured form, rather than as a free molecule, enhances its specific toxicity. The selectivity of the antifolate nanovectors can be optimized by the design of a hybrid folate/antifolate coloaded nanovector for the specific targeting of folate receptor alpha, which is overexpressed on numerous cancer cell types
Design of graphene based PVA composites for biomedical devices
Full text linkThis work conducted within Prof. Paradossi’s group at the Department of Chemical Science and Technology in the University of Rome Tor Vergata aimed to develop an easily applicable strategy enabling functionalization of graphene, suspended in an aqueous medium in its pristine form, to biocompatible polymeric surfaces, in particular “poly(vinylalcohol)”platforms, designed for biomedical applications. Nowadays graphene, this new two-dimensional material with fascinating properties, is emerging in many scientific fields. Exploitation of graphene propertieshas been one of the motivations to implement biomedical applications of interest for our laboratory. Ourinvestigations are aboutwhat kind of functionalities can be introduced ina polymeric platform, such as hydrogel sponges for anti-tumor drug delivery or the surface of microbubbles, still inthedevelopment phase as multimodal imaging contrast agents mainly for ultrasoundsand photoacoustics. To this regard, photoacoustic imaging is a high-resolution preclinical fast developing diagnostic tool. Evolution of this imaging methodology can bring to a new clinical tool designed for human investigationandis a major challenge that can be tackled by ad hocengineered contrast agents. To this aiman optimized selection of advanced hybrid platforms is needed. Graphene derivatives, mainly graphene oxide (GO) and reduced graphene oxide (RGO),exhibiting depleted properties with respect to pristine graphene, but chemically more versatile, have beenhighlighted in the recent literature. These forms derive from the chemical modifications of the 2D structure of graphene in very harsh conditions, which introduce kinks and irregularities in the carbonic material. Such modifications make GO and RGO more reactive and more processable than pristine graphene, but jeopardize the electrical, optical and mechanical properties of this material. Despite this fact, we have not found a study thatreports theincorporation of pristine graphene into biomedical devicesstarting from its suspended form in aqueous media. The challenge herein was to preserve the graphene original properties which are important for the applications we address;and find the intermediate key to adequately tether graphene on our studied poly(vinylalcohol) composites. For this, Prof. Paradossi’s group strong background about poly(vinylalcohol) hydrogels and microbubbles was a great advantage.The first chapter of the thesis is a brief general introduction about graphene and poly(vinylalcohol) providing the necessary details of why these materials could be interesting candidates for our research, taking into accountthe main problems concerning the separate materials as well as their assembly and formulatinghypothesis regarding the efficiency and biocompatibilityof the hybrid systems.The second chapter is a proof of concept on the method allowing pristine graphene entrapment into a poly(vinylalcohol) hydrogel matrix with potential in drug release at physiological temperature by using thermosensitive moieties.The third chapter of this thesisis a general introduction to the photoacoustic imaging. It provides the basic theoretical foundation for understanding this method and the physical mechanisms related to photoacoustic generation in biological tissues. First, we describe light propagation mechanisms in tissues, and the deposition of heat via optical absorption. Assimilating the biological tissue to a liquid medium, wethen introduce the fundamental equations describing the photoacoustic issue, and the assumptions used in imaging to improve diagnosis. We also introduce ultrasound imaging and its inherent clinical approach for diagnostic and therapy. Finally, the contrast agents used in both ultrasound and photoacoustic imaging modalities are discussed through two important examples: microbubbles and NIR absorbing agents. The chapter IV details the state of the art in the context of the objectives we pursued during this thesis regarding hybrid contrast agents for photoacoustic imaging based pristine graphene and poly(vinylalcohol) microbubbles. Details on the microdevice fabrication as well as its physico-chemical characterization are provided. Finally, the potential of the graphene poly(vinylalcohol) microbubbles in enhancing the photoacoustic signal is assessed in vitro and in vivo. In the chapter V, we present a study on the influence of diamine intermediates and PEGylation used as links between graphene and the PVA microbubbles on the colloidal behavior, acoustic properties, and cytotoxicity of the overall system.An appendix is presented at the end of the thesis describing a preliminarywork carried recently on the realization of new “phase-change”ultrasound contrast agents with a photo-polymerized surfactant monolayer shell structureencapsulating perfluorocarbon. These systems are in normal conditions droplets and upon ultrasound irradiation,they convert into microbubbles by “acoustic droplet vaporization”. The phase change efficiency is studied and the experimental setup and operating conditionsaredetailed
Injectable peptidic hydrogels for bone tissue repair and regeneration.
No full textThe ongoing growth in the incidence of bone injuries and diseases is producing an increment in the demand of medical and healthcare resources, with an urgent need to identify suitable alternatives to current common clinical treatments. In this context, bone tissue engineering is part of an emerging interdisciplinary field that applies the principles of engineering and life sciences towards the development of biological substitutes. Peptide hydrogels may be used in this context as biocompatible and biodegradable materials suitable for cell encapsulation and for the controlled spatial and temporal delivery of biomolecules (e.g. growth factors) able to direct cell differentiation.
Recently, we developed an enzymatic approach for the preparation of injectable, self-assembling materials based on Fmoc-oligopeptides1. The reaction products (Fmoc peptides) spontaneously self-assemble in water to originate fibrils, that become entangled to form a three-dimensional structure of fibers with a diameter of approximately 7 nm, as evidenced by atomic force microscopy (AFM) measurements. Macroscopically, a stable, self-supporting hydrogel material is produced. These materials can be used as controlled drug delivery systems for a wide spectrum of bioactive molecules2 and may enhance cell production of growth factors3. Our results suggest the possibility of using Fmoc oligopetides as building blocks for a new class of injectable scaffolds that could play an important role in bone regeneration, i.e. to reconstruct anatomical defects caused by cancer surgery, malformations and trauma. We employed such hydrogels for the preparation of composite materials specifically designed for bone tissue regeneration. These tailor-made hydrogel systems contain biopolymeric spheres delivering bioactive molecules, as well as pure and substituted calcium phosphate (CaP) nanoparticles to provide bioactivity, osteoconductivity and improved mechanical properties. The morphological and viscoelastic properties of the synthesized hydrogels were investigated and their biocompatibility with different mammalian cells was assessed. Ongoing work is aimed at investigating the biological properties of the composite hydrogel systems, in terms of adhesion, growth and differentiation of human mesenchymal stem cells
Biofabrication of genipin-crosslinked peptide hydrogels and their use in the controlled delivery of Naproxen
No full textThe synthesis and optimization of peptide-based hydrogel materials have gained growing interest in the last years, thanks to their properties, that make them appealing for diverse biotechnological applications, with a particular focus in the field of biomedicine. The self-assembling abilities of low molecular weight peptides make them ideal for designing advanced materials using mild reaction conditions. In this work, a biocatalytic approach has been used for the synthesis of an Fmoc-tripeptide that is able to self-assemble in water affording a self-supporting hydrogel. The mechanical properties of this material have been enhanced through chemical crosslinking by using a natural compound, genipin, that allows to minimize cytotoxic effects. Moreover, we have tested the potential of the prepared materials to be employed as drug delivery systems using naproxen as an anti-inflammatory model drug, and studying its release kinetics in aqueous medium. The cytotoxicity of the hydrogels has been evaluated, and their mechanical and morphological properties have been studied by rheology and SEM microscopy
Biosynthesis and characterization of a novel Fmoc-tetrapeptide based hydrogel for biotechnological applications
No full textThe applications of peptide-based materials are currently expanding, especially in the biomedical field. The biocompatibility and biodegradability of peptide materials, as well as their ability to assemble into ordered secondary structures, are indeed ideal for biotechnological applications. However, their full potential will be exploited once novel synthetic procedures are developed for advanced applications. In this work, we explored the ability of Pseudomonas fluorescens lipase to biosynthesize the self-assembled tetrapeptide FmocPheGlyPhe2 for tissue regeneration. In gel phase, these self-assembling tetrapeptides form a long interconnected nanofibrillar network, as is evident from SEM analysis. Mass spectrometry analysis was used to verify the in vitro formation of the tetrapeptide. Moreover, we characterized the rheological and chemico-physical properties of the obtained materials and studied their in vitro biocompatibility with mammalian fibroblasts. © 2017 Elsevier B.V
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Biosynthesis and Characterization of Cross-Linked Fmoc Peptide-Based Hydrogels for Drug Delivery Applications
Full text linkRecently, scientific and technological interest in the synthesis of novel peptide-based hydrogel materials have grown dramatically. Applications of such materials mostly concern the biomedical field with examples covering sectors such as drug delivery, tissue engineering, and production of scaffolds for cell growth, thanks to their biocompatibility and biodegradability. In this work we synthesized Fmoc-Phe3 based hydrogels of different chirality by using a biocatalytic approach. Moreover, we investigated the possibility of employing a crosslinker during the biosynthetic process and we studied and compared some chemico-physical features of both crosslinked and non-crosslinked hydrogels. In particular, we investigated the rheological properties of such materials, as well as their swelling ability, stability in aqueous medium, and their structure by SEM and AFM analysis. Crosslinked and non-crosslinked hydrogels could be formed by this procedure with comparable yields but distinct chemico-physical features. We entrapped dexamethasone within nanopolymeric particles based on PLGA coated or not with chitosan and we embedded these nanoparticles into the hydrogels. Dexamethasone release from such a nanopolymer/hydrogel system was controlled and sustained and dependent on genipin crosslinking degree. The possibility of efficiently coupling a drug delivery system to hydrogel materials seem particularly promising for tissue engineering applications, where the hydrogel could provide cells the necessary support for their growth, while nanoparticles could favor cell growth or differentiation by providing them the necessary bioactive molecules
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