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WIREs Nanomed Nanobiotechnol
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Polymeric nanoparticles: the future of nanomedicine

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Polymeric nanoparticles (NPs) are one of the most studied organic strategies for nanomedicine. Intense interest lies in the potential of polymeric NPs to revolutionize modern medicine. To determine the ideal nanosystem for more effective and distinctly targeted delivery of therapeutic applications, particle size, morphology, material choice, and processing techniques are all research areas of interest. Utilizations of polymeric NPs include drug delivery techniques such as conjugation and entrapment of drugs, prodrugs, stimuli‐responsive systems, imaging modalities, and theranostics. Cancer, neurodegenerative disorders, and cardiovascular diseases are fields impacted by NP technologies that push scientific boundaries to the leading edge of transformative advances for nanomedicine. WIREs Nanomed Nanobiotechnol 2016, 8:271–299. doi: 10.1002/wnan.1364

Historical timeline of therapeutic nanosystems. [PLGA‐PEG NPs, poly(lactic‐co‐glycolic acid)‐polyethyleneglycol nanoparticles; Doxil, first Food and Drug Administration‐approved liposome; Ferumoxide, iron oxide magnetic resonance imaging contrast agent; Abraxane, protein‐based drug delivery system; Genexol‐PM, polymeric micelle; CALAA‐01, targeted cyclodextrin–polymer hybrid; BIOD‐014, targeted polymeric nanoparticle, Accurint Technology; SEL‐068, fully integrated polymeric nanoparticle vaccines, tSVPt Technology; DXTL‐TNP, docetaxel‐targeted nanoparticle; DOX‐BASP NPs, acid‐degradable doxorubicin brush‐arm star polymer nanoparticles, in vitro work]. (From,97 reprinted with permission from AAAS) (Adapted with permission from Ref . Copyright 2014 American Chemical Society) (Reprinted with permission from Ref . Copyright 2012 The Royal Society of Chemistry)
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This figure demonstrates two applications of polymeric NPs in molecular imaging. (a1) Whole‐body near‐infrared (NIR) imaging of CT‐26 tumor‐bearing mice postinjection of free indocyanine green (ICG) and ICG‐loaded pluronic‐127 micelles. (a2) This graph shows fluorescence efficiency of free ICG and ICG‐loaded pluronic‐127 micelles in different organs. (Reprinted with permission from Ref . Copyright 2010 Springer). (b1) Serial axial X‐ray computed tomography (CT) images display strong signals in tumors in mice 4 h after intratumoral injection of poly(iohexol) nanoparticles (NPs). (b2) X‐ray CT images of coronal in MCF‐7 xenografts‐bearing mice, which show slower renal clearance for poly(iohexol) NPs compared to iohexol. (b3) Bar graph shows enhanced density (ΔHU) versus time for tumors after injection of poly(iohexol) NPs or iohexol. (b4) Fluoroscopic images of mice after jugular vein injection of iohexol and poly(iohexol) NP. (b5) Graph shows in vivo circulation time of iohexol (short circulation half‐life; 3.8 h) and poly(iohexol) NPs (long circulation half‐life; 15.9 h). (Reprinted with permission from Ref . Copyright 2013 American Chemical Society)
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An overview of the prodrug concept. (a) A representation of a drug promoiety, which is the prodrug that is typically pharmacologically inactive. (b) Prodrug design options with common functional groups shown in green. (Reprinted with permission from Ref . Copyright 2008 Macmillan Publishers Ltd)
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Examples of pH and dual responsive polymeric NPs. (a1) This graph demonstrates cumulative release of doxorubicin (DOX) from polymeric nanoparticles (NPs) at different pH values. (a2) Cellular uptake of NPs (red) at different pH values. Images were taken after loading the NPs for 1 h. (a3) Subcellular distribution of NPs (red) at pH 6.8 for different culture time. (Reprinted with permission from Ref . Copyright 2011 American Chemical Society). (b1) This schematic shows the formation and structural changes of the dual‐sensitive DOX‐loaded highly packed interlayer‐crosslinked micelle (HP‐ICMS). (b2) Fluorescence images of accumulation of DOX‐loaded micelles in Bel‐7402 tumor after tail vein injection of NPs. (b3) This graph shows volume changes of the Bel‐7402 tumor in mice after injection of different micelle formulations. (Reprinted with permission from Ref . Copyright 2011 WILEY‐VCH Verlag GmbH & Co. KGaA)
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Characteristics of polymeric nanoparticles based on particle size and morphology. (Reprinted with permission from Ref . Copyright 2012 The Royal Society of Chemistry)
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Nanoparticle distribution within the atherosclerotic vessel wall. (a) No fluorescent signal observed in control vessels, whereas the atherosclerotic vessel wall contained a substantial amount of NPs (in red). (b) High‐resolution transmission electron microscopy displays endothelial cells (ECs) with an endothelia gap between ECs and a macrophage (MΦ). Some individual nanoparticles can be observed within vesicles of MΦ next to endothelial gaps. Nanoparticles can also be found in the neovessel (N) within the plaque bordered by a lipid‐loaded MΦ. (Reprinted with permission from Ref . Copyright 2014 Proceedings of the National Academy of Sciences)
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Various preparation techniques for polymer nanoparticles. (Reprinted from permission from Ref . Copyright 2011 Elsevier)
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Micrographs of particle shapes made by using a mechanical stretching technique. (a) Spheres, (b) rectangular disks, (c) rods, (d) worms, (e) oblate ellipses, (f) elliptical disks, (g) unidentified flying objects (UFOs), and (h) circular disks (scale bars: 2 µm). (Reprinted with permission from Ref . Copyright 2007 National Academy of Sciences, U.S.A.)
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The biological barriers present in the body cause variable processes (both passive and active) to occur for particle transport. The distribution and clearance of particles vary based on the size of the particle. (Reprinted with permission from Ref . Copyright 2009 Macmillan Publishers Ltd)
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