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      Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles

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          Abstract

          Nanoparticulate drug/gene carriers have gained much attention in the past decades because of their versatile and tunable properties. However, efficacy of the therapeutic agents can be further enhanced using naturally occurring materials‐based nanoparticles. Polysaccharides are an emerging class of biopolymers; therefore, they are generally considered to be safe, non‐toxic, biocompatible and biodegradable. Considering that the target of nanoparticle‐based therapeutic strategies is localization of biomedical agents in subcellular compartments, a detailed understanding of the cellular mechanism involved in the uptake of polysaccharide‐based nanoparticles is essential for safe and efficient therapeutic applications. Uptake of the nanoparticles by the cellular systems occurs with a process known as endocytosis and is influenced by the physicochemical characteristics of nanoparticles such as size, shape and surface chemistry as well as the employed experimental conditions. In this study, we highlight the main endocytosis mechanisms responsible for the cellular uptake of polysaccharide nanoparticles containing drug/gene.

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          Polysaccharides-based nanoparticles as drug delivery systems.

          Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery systems. In particular, polysaccharides seem to be the most promising materials in the preparation of nanometeric carriers. This review relates to the newest developments in the preparation of polysaccharides-based nanoparticles. In this review, four mechanisms are introduced to prepare polysaccharides-based nanoparticles, that is, covalent crosslinking, ionic crosslinking, polyelectrolyte complex, and the self-assembly of hydrophobically modified polysaccharides.
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            Mechanisms of Cellular Uptake of Cell-Penetrating Peptides

            Recently, much attention has been given to the problem of drug delivery through the cell-membrane in order to treat and manage several diseases. The discovery of cell penetrating peptides (CPPs) represents a major breakthrough for the transport of large-cargo molecules that may be useful in clinical applications. CPPs are rich in basic amino acids such as arginine and lysine and are able to translocate over membranes and gain access to the cell interior. They can deliver large-cargo molecules, such as oligonucleotides, into cells. Endocytosis and direct penetration have been suggested as the two major uptake mechanisms, a subject still under debate. Unresolved questions include the detailed molecular uptake mechanism(s), reasons for cell toxicity, and the delivery efficiency of CPPs for different cargoes. Here, we give a review focused on uptake mechanisms used by CPPs for membrane translocation and certain experimental factors that affect the mechanism(s).
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              Insight into nanoparticle cellular uptake and intracellular targeting.

              Collaborative efforts from the fields of biology, materials science, and engineering are leading to exciting progress in the development of nanomedicines. Since the targets of many therapeutic agents are localized in subcellular compartments, modulation of nanoparticle-cell interactions for efficient cellular uptake through the plasma membrane and the development of nanomedicines for precise delivery to subcellular compartments remain formidable challenges. Cellular internalization routes determine the post-internalization fate and intracellular localization of nanoparticles. This review highlights the cellular uptake routes most relevant to the field of non-targeted nanomedicine and presents an account of ligand-targeted nanoparticles for receptor-mediated cellular internalization as a strategy for modulating the cellular uptake of nanoparticles. Ligand-targeted nanoparticles have been the main impetus behind the progress of nanomedicines towards the clinic. This strategy has already resulted in remarkable progress towards effective oral delivery of nanomedicines that can overcome the intestinal epithelial barrier. A detailed overview of the recent developments in subcellular targeting as a novel platform for next-generation organelle-specific nanomedicines is also provided. Each section of the review includes prospects, potential, and concrete expectations from the field of targeted nanomedicines and strategies to meet those expectations.
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                Author and article information

                Contributors
                Yarikhosroushahia@tbzmed.ac.ir
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                28 February 2017
                September 2017
                : 21
                : 9 ( doiID: 10.1111/jcmm.2017.21.issue-9 )
                : 1668-1686
                Affiliations
                [ 1 ] Biotechnology Research Center Tabriz University of Medical Science Tabriz Iran
                [ 2 ] Student Research Committee Tabriz University of Medical Science Tabriz Iran
                [ 3 ] Department of Pharmaceutical Nanotechnology Faculty of Pharmacy Tabriz University of Medical Science Tabriz Iran
                [ 4 ] Drug Applied Research Center Tabriz University of Medical Sciences Tabriz Iran
                [ 5 ] Department of Pharmacognosy Faculty of Pharmacy Tabriz University of Medical Sciences Tabriz Iran
                Author notes
                [*] [* ] Correspondence to : Ahmad YARI KHOSROUSHAHI

                E‐mail: Yarikhosroushahia@ 123456tbzmed.ac.ir

                Article
                JCMM13110
                10.1111/jcmm.13110
                5571529
                28244656
                bf80f041-4161-461b-8f70-40afa8a8aae8
                © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 September 2016
                : 30 December 2016
                Page count
                Figures: 10, Tables: 0, Pages: 19, Words: 12412
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                jcmm13110
                September 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.8 mode:remove_FC converted:25.08.2017

                Molecular medicine
                drug,gene,endocytosis,nanoparticle,polysaccharide
                Molecular medicine
                drug, gene, endocytosis, nanoparticle, polysaccharide

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