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WIREs Nanomed Nanobiotechnol
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Engineering multifunctional nanoparticles: all‐in‐one versus one‐for‐all

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Abstract Multifunctional nanoparticles have been developed to overcome the conventional hurdles associated with the diagnosis and treatment of disease. However, there are often caveats involved with the development and clinical translation of multifunctional nanoparticles largely regarding the notion that additional functionality increases nanoparticle complexity. Here, we discuss two design concepts, a conventional approach, ‘all‐in‐one’, and introduce the concept of ‘one‐for‐all’ to suggest that multifunctionality does not necessarily result in multicomponent complex nanoparticles. This review focuses on the design concepts of all‐in‐one and one‐for‐all with examples of each approach and a discussion on the implications for clinical translation. WIREs Nanomed Nanobiotechnol 2013, 5:250–265. doi: 10.1002/wnan.1217 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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Multifunctional porphysome nanovesicles. (a) Schematic of porphysomes formed from the self‐assembly of a single building block, porphyrin‐lipid. (b) Transmission electron microscopy (TEM) image of porphysomes. (c) Porphysomes can be used as an activatable fluorescence imaging contrast agent as demonstrated in a subcutaneous mouse xenograft. (d) Photoacoustic contrast enhanced imaging of the sentinel lymph node (red), inflowing lymph vessel (yellow), and secondary lymph vessels (cyan) 15‐min postinjection of porphysomes. Scale bar is 5 mm. (e) Positron emission tomography image 24 h after intravenous injection of 64Cu‐porphysomes in an orthotopic prostate cancer model. B indicates the bladder and white arrow indicates the tumor. (Reprinted with permission from Ref 92. Copyright 2012 John Wiley and Sons) (f) Thermal image showing porphysome accumulation in a KB subcutaneous tumor in a mouse and heating upon laser irradiation. (g) Photographs showing photothermal therapy using porphysomes in KB tumor bearing mice. (h) The large aqueous core of porphysomes can be loaded with other drugs such as the chemotherapy drug, doxorubicin. Elution fractions showing both doxorubicin and pyro emission indicate successful loading. (Reprinted with permission from Ref 89. Copyright 2011 Macmillan Publishers Ltd: Nature Materials)

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Intrinsically multifunctional gold nanocages for photoacoustic imaging and photothermal therapy. (a) Transmission electron microscopy image of pegylated gold nanocages. (b) In vivo photoacoustic images of gold nanocages for sentinel lymph node mapping before (i) and 194 min after (ii) injection; BV: blood vessel, SNL: sentinel lymph node. (Reprinted with permission from Ref 87. Copyright 2009 American Chemical Society) (c) (i) Photograph showing a subcutaneous tumor on the right flank of a mouse after intravenous injection of gold nanocages. Mice were injected with either gold nanocages (ii, iv) or saline (iii, v). Thermal images of the tumor on the right flank during laser irradiation at 1 min (ii, iii) and 5 min (iv, v). (d) 18F‐FDG PET/CT co‐registered images of mice with saline injection before (i) and after (iii) laser irradiation and mice with gold nanocage injection before (ii) and after (iv) laser irradiation. T: tumor. (Reprinted with permission from Ref 88. Copyright 2010 John Wiley and Sons)

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Iron oxide (FeO) nanoemulsions for optical, magnetic resonance (MR) imaging and therapy. (a) Schematic of nanoemulsion. (b) Transmission electron microscopy image of FeO nanoemulsions. (c) In vivo T2‐weighted MR images of nanoemulsions encapsulating prednisolone acetate valerate (PAV) ± FeO. (d) In vivo near infrared fluorescence (NIRF) images of nanoemulsions labeled with Cy‐7. (e) Photographs of mice injected with nanoemulsions ± PAV. Red circles indicate tumor region. (Reprinted with permission from Ref 76. Copyright 2011 American Chemical Society)

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Trimodal iron oxide nanoparticles (IONPs) for optical, positron emission tomography (PET) and magnetic resonance (MR) imaging. (a) Schematic representation of trimodal imaging probe. (b) Transmission electron microscopy image of IONPs in water. In vivo near infrared fluorescence (NIRF) (c), PET (d), and MR (e) images of a mouse injected with trimodal IONPs. White arrows indicate tumor region. (Reprinted with permission from Ref 69. Copyright 2010 Elsevier)

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Schematic representation of ‘all‐in‐one’ and ‘one‐for‐all’ design approaches for multifunctional nanoparticles. All‐in‐one (left) involves combining different agents (drug loading, imaging, etc.) into a single nanoparticle comprising of many different parts. A one‐for‐all approach (right) is based on a single building block that possesses inherent multifunctional properties.

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Expanding the use of inherently multifunctional porphyrin‐phospholipid to other nano‐ and micro‐medicine platforms. (a) Schematic representation of manganese porphyrin‐lipid (MnPL) used to stabilize and as a Raman dye for surface‐enhanced Raman scattering (SERS). (b) Surface‐enhanced Raman spectrum of MnPL gold nanoparticles in solution and in cells. (Reprinted with permission from Ref 97. Copyright 2012 American Chemical Society) (c) Schematic diagram of porphyrin shell microbubbles (‘porshe microbubbles'). (d) Ultrasound contrast mode image of a MDA‐MB231 xenograft bearing mouse before and after porshe microbubble injection. Inset image: B‐mode imaging showing soft tissue. Scale bar is 1 cm. (e) Photoacoustic images of microbubbles formed without porphyrin‐lipid and porshe microbubbles in solution. (Reprinted with permission from Ref 98. Copyright 2012 American Chemical Society)

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Multimodal CT/MR liposomal contrast agent. (a) Schematic diagram of liposome‐loaded iohexol and gadoteridol. Source: Courtesy of Dr. Jinzi Zheng. (b) Pharmacokinetics of free iohexol (filled square) and gadoteridol (filled circle) and liposomal‐encapsulated iohexol (empty square) and gadoteridol (empty circle) in mice. (c) Contrast‐enhanced in vivo CT and MR images of white rabbits before and after injection of CT/MR liposomes with observed changes in the heart (H), aorta (A), vena cava (V), carotid artery (C), kidney (K), and spleen (S). (Reprinted with permission from Ref 78. Copyright 2007 Springer Science and Business Media)

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Silica‐supported lipid bilayer nanoparticles (‘protocells’). (a) Schematic diagram protocells for targeted delivery of multicomponent cargo. (b) Cryogenic transmission electron microscopy image of protocells. Arrows indicate a 4‐nm‐thick lipid bilayer. Scale bar is 25 nm. (c) Hyperspectral confocal fluorescence microscopy of Hep3B cells 15 min (c) and 4 h (d) after incubation with multicomponent loaded protocells. Punctate signal at 15 min indicates that all components of the protocell are within the endosomes (c), whereas after 4 h, the cargo and all components of the protocell have been released into the cytosol. (Reprinted with permission from Ref 80. Copyright 2011 Macmillan Publishers Ltd: Nature Materials)

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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Emerging Technologies

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