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      A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

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          Abstract

          The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis. This advancement can be reached through the use of multimodal tracers, and nanotechnology-based solutions allow the simultaneous delivery of different diagnostic compounds moving a step towards their safe administration for multimodal imaging acquisition. Among different processes, nanoprecipitation is a consolidate method for the production of nanoparticles and its implementation in microfluidics can further improve the control over final product features accelerating its potential clinical translation. A Hydrodynamic Flow Focusing (HFF) approach is proposed to produce through a ONE-STEP process Multimodal Pegylated crosslinked Hyaluronic Acid NanoParticles (PEG-cHANPs). A monodisperse population of NPs with an average size of 140 nm is produced and Gd-DTPA and ATTO488 compounds are co-encapsulated, simultaneously. The results showed that the obtained multimodal nanoparticle could work as MRI/Optical imaging probe. Furthermore, under the Hydrodenticity effect, a boosting of the T1 values with respect to free Gd-DTPA is preserved.

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          Going deeper than microscopy: the optical imaging frontier in biology.

          Optical microscopy has been a fundamental tool of biological discovery for more than three centuries, but its in vivo tissue imaging ability has been restricted by light scattering to superficial investigations, even when confocal or multiphoton methods are used. Recent advances in optical and optoacoustic (photoacoustic) imaging now allow imaging at depths and resolutions unprecedented for optical methods. These abilities are increasingly important to understand the dynamic interactions of cellular processes at different systems levels, a major challenge of postgenome biology. This Review discusses promising photonic methods that have the ability to visualize cellular and subcellular components in tissues across different penetration scales. The methods are classified into microscopic, mesoscopic and macroscopic approaches, according to the tissue depth at which they operate. Key characteristics associated with different imaging implementations are described and the potential of these technologies in biological applications is discussed.
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            Applications of nanoparticle systems in drug delivery technology

            The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500 nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient’s compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.
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              Microfluidic platform for controlled synthesis of polymeric nanoparticles.

              A central challenge in the development of drug-encapsulated polymeric nanoparticles is the inability to control the mixing processes required for their synthesis resulting in variable nanoparticle physicochemical properties. Nanoparticles may be developed by mixing and nanoprecipitation of polymers and drugs dissolved in organic solvents with nonsolvents. We used rapid and tunable mixing through hydrodynamic flow focusing in microfluidic channels to control nanoprecipitation of poly(lactic- co-glycolic acid)- b-poly(ethylene glycol) diblock copolymers as a model polymeric biomaterial for drug delivery. We demonstrate that by varying (1) flow rates, (2) polymer composition, and (3) polymer concentration we can optimize the size, improve polydispersity, and control drug loading and release of the resulting nanoparticles. This work suggests that microfluidics may find applications for the development and optimization of polymeric nanoparticles in the newly emerging field of nanomedicine.
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                Author and article information

                Contributors
                EnzaTorino-enza.torino@unina.it
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                7 April 2020
                7 April 2020
                2020
                : 10
                : 6028
                Affiliations
                [1 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, University of Naples Federico II, Department of Chemical, Materials and Production Engineering (DICMaPI), ; P.le Tecchio 80, 80125 Naples, Italy
                [2 ]Fondazione Istituto Italiano di Tecnologia, IIT, Largo Barsanti e Matteucci 53, 80125 Naples, Italy
                [3 ]ISNI 0000 0001 0790 385X, GRID grid.4691.a, Interdisciplinary Research Center on Biomaterials, CRIB, University of Naples Federico II, ; P.le Tecchio 80, 80125 Naples, Italy
                Author information
                http://orcid.org/0000-0002-8905-1925
                Article
                63234
                10.1038/s41598-020-63234-x
                7138812
                32265496
                894185e2-8817-464b-a405-2280e43b2eba
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 July 2019
                : 27 March 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003407, Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research);
                Award ID: 2017MHJJ55
                Award Recipient :
                Categories
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                Custom metadata
                © The Author(s) 2020

                Uncategorized
                medical imaging,biomedical engineering,microfluidics,nanotechnology in cancer
                Uncategorized
                medical imaging, biomedical engineering, microfluidics, nanotechnology in cancer

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