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WIREs Nanomed Nanobiotechnol
Impact Factor: 6.14

Shaping the future of nanomedicine: anisotropy in polymeric nanoparticle design

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Nanofabrication and biomedical applications of polymeric nanoparticles have become important areas of research. Biocompatible polymeric nanoparticles have been investigated for their use as delivery vehicles for therapeutic and diagnostic agents. Although polymeric nanoconstructs have traditionally been fabricated as isotropic spheres, anisotropic, nonspherical nanoparticles have gained interest in the biomaterials community owing to their unique interactions with biological systems. Polymeric nanoparticles with different forms of anisotropy have been manufactured using a variety of novel methods in recent years. In addition, they have enhanced physical, chemical, and biological properties compared with spherical nanoparticles, including increased targeting avidity and decreased nonspecific in vivo clearance. With these desirable properties, anisotropic nanoparticles have been successfully utilized in many biomedical settings and have performed superiorly to analogous spherical nanoparticles. We summarize the current state‐of‐the‐art fabrication methods for anisotropic polymeric nanoparticles including top‐down, bottom‐up, and microfluidic design approaches. We also summarize the current and potential future applications of these nanoparticles, including drug delivery, biological targeting, immunoengineering, and tissue engineering. Ongoing research into the properties and utility of anisotropic polymeric nanoparticles will prove critical to realizing their potential in nanomedicine. WIREs Nanomed Nanobiotechnol 2016, 8:191–207. doi: 10.1002/wnan.1348 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
A wide repertoire of particle shapes can be produced with the thin film stretching method. (a) Spherical, (b) rectangular disk, (c) prolate ellipsoidal, (d) worm‐like, (e) oblate ellipsoidal, (f) prolate ellipsoidal disk, (g) UFO‐like, (h) flattened circular disk, (i) wrinkled prolate ellipsoidal, (j) wrinkled oblate ellipsoidal, and (k) porous prolate ellipsoidal particles can all be synthesized by liquefaction in a thin film and mechanical stretching. The technology is also translatable to the (l) nanoscale as the size of the particle is determined by bulk spherical particle synthesis. Scale bars are 2 µm. (Reprinted with permission from Ref . Copyright 2007 National Academy of Sciences of the USA)
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Nonspherical particles mediate better specific adhesion under flow and enable enhanced in vivo targeting. (a) Number of particles adhered at the inlet of a microfluidic device of targeted (OVA‐mAb) and nontargeted (IgG) rods (R) and spheres (S) under different shear rates. (b) Number of particles attached at the bifurcation of the device to simulate the bifurcation of a blood vessel. Increased specific adhesion and decreased nonspecific adhesion are evident for rods versus spheres. (c) Increased accumulation of ICAM‐targeted rods in the liver compared to spheres measured by lung‐to‐liver accumulation ratio. (d) Increased ratio of rod‐shaped transferrin receptor‐targeted particle to equivalent spherical particle accumulation in the brain indicates enhanced in vivo targeting capabilities of rods compared to spheres. (Reprinted with permission from Ref . Copyright 2013 National Academy of Sciences of the USA)
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Nonspherical polymeric nanoparticles can be synthesized by nanoprecipitation of polymer in a focus flow microfluidic device. (a) A solution of polymer is injected into the inlet along with two other flanking streams to focus polymer solution. Subsequent solvent exchange results in the nanoprecipitation of particles. (b) By controlling the ratio of focus solution flow and polymer solution flow, the aspect ratio and size of the nanoparticles can be tuned as desired. (c) transmission electron microscopy (TEM) images of particles produced with increasing flow ratios of the two inlet solutions. Nonspherical particles of nanoscale size are successfully produced by this method. (Reprinted with permission from Ref . Copyright 2012 American Chemical Society)
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Nonspherical stripped nanoparticles can be synthesized from the gold nanoparticle‐based surfactant dissolution of a layer block copolymer. (a) The main driving force behind the formation of this particle from a layered spherical particle is the administration of a smaller gold nanoparticle with a cross‐linked polymer shell and polystyrene on the surface. (b) Stripped ellipsoidal nanoparticles can be formed through this emulsion‐based bottom‐up process. (c and d) Zoomed in and rotated transmission electron microscopy (TEM) micrographs of the particle demonstrate how the gold acts as a surfactant for only one of the two polymer layers. (e and f) Cross‐sections of the particle at different orientations illustrate the localization of the gold nanoparticle surfactant to the outside of the stripped ellipsoidal nanoparticle. (Reprinted with permission from Ref . Copyright 2013 American Chemical Society)
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Shape memory and reprogramming applications are one application of nanoparticles produced from block copolymers. (a) Nonspherical and spherical microparticles utilized as an example to explain the procedure of shape reprogramming. (b) Schematic of temporary shape reprogramming process utilized. Particles are stretched to a nonspherical shape at the ‘temporary reprograming’ temperature and upon heating the particles reassume their spherical shape. (c) Schematic of permanent reprogramming and shape memory reversion to ellipsoidal particles. Spherical particles are first stretched to prolate ellipsoids at the ‘permanent reprogramming’ temperature, followed by stretching to oblate ellipsoids at the ‘temporary reprogramming’ temperature. Upon heating, the oblate ellipsoid assumes the permanently programmed prolate ellipsoid shape. Similar trends were seen with nanoparticles in the study. (Reprinted with permission from Ref . Copyright 2013 John Wiley and Sons)
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Emerging Technologies

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