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WIREs Nanomed Nanobiotechnol
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Nanomedical engineering: shaping future nanomedicines

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Preclinical research in the field of nanomedicine continues to produce a steady stream of new nanoparticles with unique capabilities and complex properties. With improvements come promising treatments for diseases, with the ultimate goal of clinical translation and better patient outcomes compared with current standards of care. Here, we outline engineering considerations for nanomedicines, with respect to design criteria, targeting, and stimuli‐triggered drug release strategies. General properties, clinical relevance, and current research advances of various nanomedicines are discussed in light of how these will realize their potential and shape the future of the field. WIREs Nanomed Nanobiotechnol 2015, 7:169–188. doi: 10.1002/wnan.1315 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Combinatorial criteria to be considered when designing nanoparticles. These include the class of nanoparticle size, shape, surface charge, targeting, and activation mechanism. Each factor affects the efficiency. Class determines the basic properties of the particle. Size, shape, surface charge, and targeting generally affect pharmacokinetics and biodistribution. Activation can provide improved distribution or bioavailability of encapsulated drugs.
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Heat‐triggered drug release. Specially designed Thermodox liposomes extravasate into the tumor through pores in leaky tumor blood vessels (a). Hyperthermia increases the blood vessel pore sizes (b). Hyperthermia triggers drug release from the liposomes in both the tumor blood vessels (c) and the tumor tissue (d). Hyperthermia itself can also be toxic to cancer cells (e). (Reprinted with permission from Ref . Copyright 2000 American Association for Cancer Research)
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Protease‐activated drug delivery. Multistage quantum dot gelatin nanoparticles (QDGelNPs) experience a size reduction through cleavage of their gelatin scaffold by matrix metalloproteinase 2 (MMP‐2), a protease that is highly expressed in tumors. (Reprinted with permission from Ref . Copyright 2011 National Academy of Sciences)
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Schematic of lipase‐cleavable docetaxel prodrug concept. In this system, a lipophilic enzymatically cleavable prodrug is entrapped in the phospholipid layer of the nanoparticle. The nanoparticle is targeted to cells through contact‐facilitated drug delivery where the phospholipid layer of the nanoparticle fuses with the cell membrane. The prodrug is then transferred into the cell where it undergoes enzymatic cleavage. (Reprinted with permission from Ref . Copyright 2014 Ivyspring)
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Cryo‐transmission microscopy images of Dox–PoP‐liposomes before and after light irradiation. Arrows indicate the presence of doxorubicin sulfate crystals. While the crystals are present in the ‘before’ images they are not in the after images, indicating dissolution of the crystals and release of the drug under light irradiation with minimal effect on the morphology of the nanoparticles. (Reprinted with permission from Ref . Copyright 2014 Macmillan Publishers)
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Red blood cell (RBC)‐membrane‐coated polymeric nanoparticles. RBC membranes are isolated from the intracellular contents. The isolated RBC membranes are then fused to the polymeric nanoparticles with the aim of creating particles with increased circulation time. (Reprinted with permission from Ref . Copyright 2008 National Academy of Sciences)
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(a) Filomicelles, self‐assembled diblock copolymers; yellow/green indicates hydrophobic polymer center, orange/blue indicates hydrophilic polymer (left), fluorescence imaging of a single filomicelle showing its long size. (b) Scanning electron microscopic (SEM) images of particles produced by PRINT technology; cubic particles, hydrogel boomerangs, hydrogel toroids, and hydrogel rods. (c) Schematic of liposome‐enclosed DNA nano‐octahedron (DNO). The liposomes are fused to the DNO through DNA lipid complexes that bind the liposome bilayer to the DNO. This system uses the PEGylated liposomes to function as a viral‐like capsid shell to protect the nanoparticle. (Reprinted with permission from Ref . Copyright 2007 Macmillan Publishers; Ref . Copyright 2011 John Wiley and Sons; and Ref . Copyright 2014 American Chemical Society)
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In vivo fate of nanoparticles following systemic administration. Small nanoparticles can be cleared by the kidneys, whereas larger nanoparticles can be cleared by the liver and spleen. Nanoparticles then extravasate into the tumor tissue owing to the large fenestrations in the tumor vasculature. Extravasated nanoparticles deliver drugs to target cells through endocytosis or through the breakdown of the nanoparticles and release of the drug.
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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Diagnostic Tools > In Vitro Nanoparticle-Based Sensing

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