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WIREs Nanomed Nanobiotechnol
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Protein–quantum dot nanohybrids for bioanalytical applications

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Quantum dots (QDs) coupled with biomolecules play an important role as optically and chemically stable bioimaging agents for various applications. These inorganic–biological hybrid conjugates have been demonstrated as powerful fluorescence tools for sensing, diagnostics, and labeling. This review focuses on protein–QD nanohybrids for different types of bioanalytical applications. There are various strategies to modify the surface properties of QDs to produce protein–QD nanohybrids that are stable in biological fluids. We expect that multifunctional protein–QD nanohybrids can be used as a powerful optical probe for various biological applications. WIREs Nanomed Nanobiotechnol 2016, 8:178–190. doi: 10.1002/wnan.1345 This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Schematic illustration of one‐step preparation of protein‐functionalized quantum dots (QDs). Schematic structures of proteins used as coligand for QDs. Bovine serum albumin (BSA), lysozyme, trypsin, hemoglobin, and transferrin (from left). Zn2+, Hg2+, and HSe ions were used as precursors. The synthesis was conducted at room temperature and completed in 1 second.
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(a) Schematic illustration of the microchannel network: (1) a polydimethylsiloxane (PDMS) piece was placed in a silanized slide, (2) the solutions were flowed through the channels, and the first layer of protein was immobilized, (3) the first PDMS piece was removed, (4) another PDMS piece was placed on the substrate with channels perpendicular to the first PDMS piece, (5) other solutions were flowed, (6) a two‐dimensional array was formed above the chip. (b) Schematic illustration of a sandwich immunoassay and reverse phase immunoassay based on quantum dot (QD)‐IgG fluorescent probes and a microfluidic protein chip. (Reprinted with permission from Ref Copyright 2010 ACS Publications.)
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Cellular imaging of the quantum dot (QD)‐mOrange pH sensor. (a) Schematic description of probe color changes during progression through the endocytic pathway. Förster resonance energy transfer (FRET) efficiency is high in the neutral pH of the extracellular environment and an early endosome. FRET efficiency decreases as the endosome matures and the endosomal pH drops, resulting in diminished emission from mOrange and recovery of the QD signal. Any probe that escapes from the endosome regains its elevated FRET efficiency in the pH neutral cytoplasm. (b) Fluorescence microscopy images taken immediately after addition of the probe and after incubation for 2 h. The QD images (left) demonstrate consolidation of the probe in the endosome over time; images of the direct excitation of mOrange (center) and FRET emission (right) indicate a clear decrease in the mOrange emission and the FRET efficiency of the probe with maturation of the endosome. (Reprinted with permission from Ref Copyright 2012 ACS Publications.)
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(a) Schematic illustration of the formation of albumin/functionalized quantum dot (QD) decorated folic acid. (b) The transmission electron microscopy (TEM) images of the albumin/QD in deionized water. (c) Photograph of the (1) CIS/ZnS QDs dispersed in dichloromethane, (2) CIS/ZnS‐PEG, (2) CIS/ZnS‐HSA‐PEG NCs, and (4) CIS/ZnS‐HSA‐PEG‐FA NCs under UV illumination at 365 nm. (d) The long‐term dispersion stability of the CIS/ZnS‐PEG, CIS/ZnS‐HSA‐PEG, and CIS/ZnS‐HSA‐PEG‐FA NCs, measured by the time‐dependent changes of absorbance at 500 nm in a 10% serum‐containing medium. (e) In vivo fluorescence images of a HeLa tumor‐bearing mouse after intravenous injection of CIS/ZnS‐HSA‐PEG‐FA NCs in phosphate buffered solution (PBS). The area circled in red indicates the implanted tumor site. Whole‐body fluorescence images of each mouse were acquired from an IVIS® Xenogen imaging system. (Reprinted with permission from Ref Copyright 2014 IOP Publishing.)
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