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WIREs Nanomed Nanobiotechnol
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Emerging methods in therapeutics using multifunctional nanoparticles

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Abstract Clinical translation of nanoparticle‐based drug delivery systems is hindered by an array of challenges including poor circulation time and limited targeting. Novel approaches including designing multifunctional particles, cell‐mediated delivery systems, and fabrications of protein‐based nanoparticles have gained attention to provide new perspectives to current drug delivery obstacles in the interdisciplinary field of nanomedicine. Collectively, these nanoparticle devices are currently being investigated for applications spanning from drug delivery and cancer therapy to medical imaging and immunotherapy. Here, we review the current state of the field, highlight opportunities, identify challenges, and present the future directions of the next generation of multifunctional nanoparticle drug delivery platforms. This article is categorized under: Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Techniques for the synthesis of multifunctional nanoparticles. (a) Vapor‐assisted deposition of macromolecules to select areas of nanoparticles through matrix assisted pulsed laser evaporation. Scale bar, 200 nm. Adapted with permission from Shepard, Christie, Sosa, Arnold, and Priestley (). (b) Layer‐by‐layer (LBL) fabrication of polymer‐coated, hollow silica nanoparticles for temporally controlled release of encapsulated drugs. Scale bar, 100 nm. Adapted with permission from Palanikumar et al. (). (c) Anisotropic, multifunctional patchy nanoparticles formed through the use of glancing angle deposition). Scale bar, 2 μm. Adapted with permission from Pawar and Kretzschmar (). (d) Tandem nanoprecipitation and internal phase separation employed to create surface‐reactive, patchy nanoparticles prepared through the use of block copolymers (BCPs) and tuning of preparation conditions. Scale bar, 100 nm. Adapted with permission from Varadharajan, Turgut, Lahann, Yabu, and Delaittre (). (e) Surface‐reactive, multicompartmental particles fabricated using electrohydrodynamic (EHD) cojetting through the spatially controlled addition of chemically orthogonal surface functional groups. Adapted with permission from Rahmani et al. (). (f) Continuous and high‐throughput synthesis of multicompartmental nanoparticles through the formation of compound droplets in flow and subsequent ultraviolet initiated crosslinking. Scale bar, 100 nm. Adapted with permission from Nie, Li, Seo, Xu, and Kumacheva ()
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Different circulatory cells used in cellular hitchhiking formulations. (a) Scanning electron micrographs of nanogels adsorbed onto the surface of murine red blood cells (RBCs) in vitro. Scale bar = 1 μm. Adapted with permission from Brenner et al. (). (b) Scanning electron micrographs of hyaluronic acid coated backpack attached to the surface of J774 mouse macrophages after 3 hr incubation in cell culture conditions. Scale bar = 5 μm. Adapted with permission from Doshi et al. (). (c) Confocal image of fluorescently labeled nanoparticles conjugated to biotinylated neural stem cell stained with calcein‐AM. Scale bar = 10 μm. Adapted with permission from Mooney, Weng, et al. (). (d) Schematic drawing of circulatory cell‐mediated targeting and delivery of nanoparticles
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Protein Nanoparticles hold great promise in medicine due to their variety and inherent functionalities. Three main methods exist to synthesize these particles. (a) Nab technology works by using a sheer mediated process to force hydrophobic drugs within proteins and subsequently cause the proteins to aggregate into nanoscale particles. (b) Self‐assembly techniques use the expression of specially designed proteins by microorganisms that subsequently self‐assemble into structures that can be used for broad variety of therapeutic applications. (c) Coacervation functions by the addition of an organic solvent or reagent to a protein solution, which causes the formation of particles that are subsequently crosslinked using bifunctional crosslinkers
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Multicompartmental protein nanoparticles can be made through electrohydrodynamic cojetting, as shown in (a). As an example, we synthesized particles with two compartments, one made of insulin and the other of hemoglobin. The particles are spherical as shown in the electron micrograph in (b), and show a clear bicompartmental nature when each compartment is selectively loaded with a fluorescent dye and imaged using structured illumination microscopy (insert). Scale bar is 200 nm
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Biology-Inspired Nanomaterials > Protein and Virus-Based Structures

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