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      MicroRNA delivery through nanoparticles

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          Abstract

          MicroRNAs (miRNAs) are attracting a growing interest in the scientific community due to their central role in the etiology of major diseases. On the other hand, nanoparticle carriers offer unprecedented opportunities for cell specific controlled delivery of miRNAs for therapeutic purposes. This review critically discusses the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of cancer and neurodegenerative disorders and for tissue regeneration. A fresh perspective is presented on the design and characterization of nanocarriers to accelerate translation from basic research to clinical application of miRNA-nanoparticles. Main challenges in the engineering of miRNA-loaded nanoparticles are discussed, and key application examples are highlighted to underline their therapeutic potential for effective and personalized medicine.

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          Most cited references 182

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          Prediction of mammalian microRNA targets.

          MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
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            Control of translation and mRNA degradation by miRNAs and siRNAs.

            The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro RNAs (miRNAs) and short interfering RNAs (siRNAs) and can affect mRNA degradation and translation, as well as chromatin structure, thereby having impacts on transcription rates. In this review, we discuss possible mechanisms by which miRNAs control translation and mRNA degradation. An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control.
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              Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine.

               A. El-Lakany,  S Lee,  P. Jain (2006)
              The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica-gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed ( approximately 40 nm) show an absorption cross-section 5 orders higher than conventional absorbing dyes, while the magnitude of light scattering by 80-nm gold nanospheres is 5 orders higher than the light emission from strongly fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres, i.e., from approximately 520 to 550 nm, is however too limited to be useful for in vivo applications. Gold nanoshells are found to have optical cross-sections comparable to and even higher than the nanospheres. Additionally, their optical resonances lie favorably in the near-infrared region. The resonance wavelength can be rapidly increased by either increasing the total nanoshell size or increasing the ratio of the core-to-shell radius. The total extinction of nanoshells shows a linear dependence on their total size, however, it is independent of the core/shell radius ratio. The relative scattering contribution to the extinction can be rapidly increased by increasing the nanoshell size or decreasing the ratio of the core/shell radius. Gold nanorods show optical cross-sections comparable to nanospheres and nanoshells, however, at much smaller effective size. Their optical resonance can be linearly tuned across the near-infrared region by changing either the effective size or the aspect ratio of the nanorods. The total extinction as well as the relative scattering contribution increases rapidly with the effective size, however, they are independent of the aspect ratio. To compare the effectiveness of nanoparticles of different sizes for real biomedical applications, size-normalized optical cross-sections or per micron coefficients are calculated. Gold nanorods show per micron absorption and scattering coefficients that are an order of magnitude higher than those for nanoshells and nanospheres. While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorods of high aspect ratio with a larger effective radius.
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                Author and article information

                Contributors
                Journal
                J Control Release
                J Control Release
                Journal of Controlled Release
                Elsevier Science Publishers
                0168-3659
                1873-4995
                10 November 2019
                10 November 2019
                : 313
                : 80-95
                Affiliations
                [a ]Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy
                [b ]Singapore-MIT Alliance for Research & Technology (SMART), BioSystems and Micromechanics (BioSyM), Singapore, Singapore 3
                [c ]Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 3
                [d ]Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research, Singapore, Singapore 3
                [e ]Department of Mechanical Engineering, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA, 02139, USA
                [f ]Department of Biological Engineering, Massachusetts Institute of Technology, 500 Technology Square, Room NE47-321, Cambridge, MA, 02139, USA
                [g ]Institute of Industrial Science, The University of Tokyo, Meguro-ku, Tokyo 153-8505, Japan 3
                [h ]Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore
                Author notes
                [* ]Corresponding authors. Clara.mattu@ 123456polito.it
                [1]

                These authors equally contributed as first authors.

                [2]

                These authors equally contributed as last authors.

                [3]

                Present addresses.

                Article
                S0168-3659(19)30579-6
                10.1016/j.jconrel.2019.10.007
                6900258
                31622695
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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