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WIREs Nanomed Nanobiotechnol
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Fluorescent hybrid silica nanoparticles and their biomedical applications

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Abstract Benefitting from the subtle combination of robust inorganic silica with organic dyes, fluorescent hybrid silica nanoparticles are getting more and more attention by virtue of their excellent aqueous solubility, superior photo‐ and chemical stability, negligible cytotoxicity, and multifunctional capability. On overcoming the disadvantages of traditional organic dyes, fluorescent hybrid silica nanoparticles have exhibited promising biomedical application potentials both in vitro and in vivo, such as bioimaging, anti‐tumor theranostics and biosensing, etc. In this review, various fluorescent hybrid materials based on colloidal silica nanoparticles, mesoporous silica nanoparticles and silica‐block copolymer hybrid micelles are discussed from the design, synthesis to their biomedical applications. Especially, the fluorescent hybrid silica/organosilica cross‐linking block copolymer micelles are introduced in detail. Finally, the prospects and challenges of these fluorescent hybrid silica nanoparticles in terms of their design, synthesis, and biomedical application are presented. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Scheme of three different synthetic routes of fluorescent colloidal silica nanoparticles: (a) “Homogeneous nucleation” process, (b) “Homogeneous nucleation” route, and (c) reverse microemulsion method
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(a) Schematic for the preparation of nanoprobe for oxygen and pH sensor, and chemical structures of the probes used. (b) pH‐dependent spectra of the dual nanosensors. (c) Oxygen‐dependent spectra of the dual nanosensors. (d) Confocal laser scanning microscopy images of the nanosensors internalized into normal rat kidney cells via electroporation. d1: green luminescence of FITC; d2: red luminescence of both TFPP and PtTPTBP; d3: NIR luminescence of nanoparticles dyed with PtTPTBP only after delivery via electroporation. (Reprinted with permission from X. D. Wang et al. (). Copyright 2012 American Chemical Society)
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(a) Schematic illustration for the fabrication and therapy mechanism of QM‐NPQ@PDHNs. (b) Morphology (b1), spectra (b2), GSH and GSTπ response characters (b3–b5) of QM‐NPQ@PDHNs. (c) The three‐dimensional fluorescence images of a tumor‐bearing mouse after intravenous injection of QM‐NPQ@PDHNs for 24 hr with an injection dose of 10 mg/kg of NPQ. (d) Changes in the tumor size of nude mice inoculated with SMMC‐7721 cells after treatment of NPQ and QM‐NPQ@PDHNs for 21 days. (Reprinted with permission from Jia et al. (). Copyright 2018 John Wiley and Sons)
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(a–c) TEM images of the as‐prepared OSNCs (inset: the size distribution and optical images of OSNCs under UV light irradiation). (d) Absorption spectra of OSNCs. (e) Confocal microscopy images of HeLa cells incubated with 50 mg/ml of OSNC‐2 (E1, E2) and OSNC‐3 (E3, E4) at 37°C for 2 hr. (Reprinted with permission from L. Yang et al. (). Copyright 2016 Royal Society of Chemistry)
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(a) Synthesis route of TPE and silole derivative containing fluorescent silica nanoparticles (FSNP‐1 and FSNP‐2). (b) TEM and SEM images of FSPN‐1 and FSPN‐2. (Inset: photographs of FSNP‐1 and FSNP‐2 ethanol suspensions under the 365 nm UV light illumination.) (c) Fluorescence images of HeLa cells incubated with FSNP‐1 and FSNP‐2 with different luminogen loadings. Concentration of luminogen (μm): C1: 2, C2: 4, C3: 8, C4: 2, C5: 4, C6: 6. (Reprinted with permission from Faisal et al. (). Copyright 2010 John Wiley and Sons)
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(a) Schematic diagram for the synthesis of CyN‐12@NHs and chemical structures of CyN‐12. (b) TEM image of CyN‐12@NHs. (c) Fluorescence spectra of CyN‐12 and CyN‐12@NHs. Red curve: CyN‐12 (5 mM) in water (2% DMSO), λex = 635 nm; blue curve: CyN‐12 (5 mM) in ethanol (2% DMSO), λex = 664 nm; black curve: CyN‐12@NHs in water, λex = 690 nm. (d) Time dependence of photobleaching of CyN‐12 (5 mM in water, 2% DMSO, monitored at 635 nm), CyN‐12@NHs (water, monitored at 690 nm), and ICG (5 mM in water, 2% DMSO, monitored at 780 nm) under constant illumination for 0–1,300 s, data were recorded every 0.5 s. (e) Absorbance changes of CyN‐12 (5 mM in water, 2% DMSO, 635 nm), CyN‐12@NHs (water, 690 nm), ICG (5 mM in water, 2% DMSO, 780 nm) upon titration of ClO (0, 5, 10, 20, 30, 50, 100, 150, and 200 mM). (f) in vivo images of a mouse injected with CyN‐12@NHs (0.5 mg/kg) via intratumor injection: 5 min (F1), 1 hr (F2), 2 hr (F3), 6 hr (F4), 24 hr (F5) after injection. The excitation and emission wavelengths are 720 and 790 nm, respectively. (Reprinted with permission from Chang et al. (). Copyright 2013 Royal Society of Chemistry)
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(a) Schematic diagram for the fabrication of QM‐2@PNPs. (b) SEM image of QM‐2. (c) TEM image of QM‐2@PNPs. in vivo images of a mouse injected with bare QM‐2 (d) and QM‐2@PNPs (e) via intravenous injection for 0.5, 2, and 24 hr and ex vivo fluorescence images of organs after injected with QM‐2@PNPs or QM‐2 for 24 hr. (Reprinted with permission from Y. Li et al. (). Copyright 2016 John Wiley and Sons)
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(a) Schematic illustration and (b) TEM images of the as‐synthesized and PTA‐stained silica cross‐linked F127 micelles. (c) Chemical structure of the fluorescent conjugated polymers and the digital photos of corresponding fluorescent hybrid silica cross‐linked micelles solution under UV illumination (λex = 254 nm). (d) Confocal microscopy images of BV‐2 microglial cells incubated with 20% (vol/vol) BP‐PPV hybrid silica cross‐linked micelles for 24 hr. (Reprinted with permission from Tan et al. (). Copyright 2009 Royal Society of Chemistry)
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Schematic illustration for the construction of fluorescent silica‐block copolymer hybrid micelles
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(a) Schematic illustration of the construction of ACQ@AIE‐PMO with tunable multicolor emission. (b) Fluorescence spectra of RhB@AIE‐PMO with different RhB content. (c) Bright‐field and (right) fluorescent images of HeLa cells after incubation with RhB@AIE‐PMO with different RhB concentrations: (c1 and c2) 0 mol%, (c3 and c4) 0.36 mol%, and (c5 and c6) 1.71 mol%. (Reprinted with permission from D. Li, Zhang, et al. (). Copyright 2015 Royal Society of Chemistry)
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Scheme of synthesizing fluorescent hybrid mesoporous silica nanoparticles
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Diagnostic Tools > In Vitro Nanoparticle-Based Sensing

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