Dye-Doped Fluorescent Silica Nanoparticles for Live Cell and In Vivo Bioimaging

Abstract

The need for novel design strategies for fluorescent nanomaterials to improve our understanding of biological activities at the molecular level is increasing rapidly. Dye-doped fluorescent silica nanoparticles (SiNPs) emerge with great potential for developing fluorescence imaging techniques as a novel and ideal platform for the monitoring of living cells and the whole body. Organic dye-containing fluorescent SiNPs exhibit many advantages: they have excellent biocompatibility, are non-toxic, highly hydrophilic, optically transparent, size-tunable and easily modified with various biomolecules. The outer silica shell matrix protects fluorophores from outside chemical reaction factors and provides a hydrophilic shell for the insoluble nanoparticles, which enhances the photo-stability and biocompatibility of the organic fluorescent dyes. Here, we give a summary of the synthesis, characteristics and applications of fluorescent SiNPs for non-invasive fluorescence bioimaging in live cells and in vivo. Additionally, the challenges and perspectives of SiNPs are also discussed. We prospect that the further development of these nanoparticles will lead to an exciting breakthrough in the understanding of biological processes.

Keywords: bioimaging; in vivo; organic fluorescent dye; silica nanoparticle.

Figure 1

Simple procedure synthesis of mesoporous silica nanoparticles.

Figure 2

(A) Procedures for preparation amine group- and TAT peptide-conjugated mesoporous silica nanoparticles (MSNs); (B) an illustration of doxorubicin (Dox)@MSNs-TAT for targeting nuclei of cancer cells and delivering/releasing drugs directly into nuclei; (C) Transmission electron microscope transmission electron microscope (TEM) images of MSNs with different sizes. Scale bars: 100 nm. Reproduced with permission from [55]. Copyright 2012 American Chemical Society.

Figure 3

(A) Chemical reaction routes of pH-responsive hierarchical poreSiNP (HPSN)-N,N-phenylenebis(salicylideneimine)dicarboxylic acid (Salphdc)-folate (FA) nanosystem; (B) the tumor therapy and bioimaging in vivo of the drug-loaded HPSN-Salphdc-FA nanosystem. Reproduced with permission from [39]. Copyright 2015 American Chemical Society.

Figure 4

(A) Whole-body real-time fluorescence imaging of DOX@HPSN-Salphdc (I) and DOX@HPSN-Salphdc-FA (II) at different hours. Scale bars: 3 cm. (B) Histogram of the fluorescence intensity of tumors issue treated with Dox@HPSN-Salphdc and Dox@HPSN-Salphdc-FA at each interval, respectively. (C) Images of mainly organs and (D) quantitative energy dispersive spectrometry analysis after injection of DOX@HPSN-Salphdc-FA for 16 h. (E) The fluorescence intensities of both nanoparticles in blood over time. The error bars indicate the mean ± SD (n = 4). * p < 0.05 and ** p< 0.01. Reproduced with permission from [39]. Copyright 2015 American Chemical Society.

Figure 5

Experimental design for the large stokes shifting NIR fluorescent SiNPs (LSS-NFSiNPs) and real-time abdomen fluorescence resonance energy transfer (FRET) imaging of mice intravenously injected with the LSS-NFSiNPs. Reproduced with permission from [30]. Copyright 2012 American Chemical Society.

Figure 6

Schematic illustration of dye-loaded mesoporous SiNPs for both NIR fluorescent and photoacoustic (PA) imaging. Reproduced with permission from [72]. Copyright 2015 American Chemical Society.

Figure 7

Schematic illustration of organically-modified two-photon photodynamic therapy SiNPs. Reproduced with permission from [74]. Copyright 2007 American Chemical Society.

Figure 8

Schematic illustration of two-photon (TP)-MSNs@MnO₂for glutathione detection. Reproduced with permission from [73]. Copyright 2014 American Chemical Society.

Figure 9

Two-photon confocal microscopy (CM) images of glutathione detection in living CEM cells. (a) CEM cells incubated with the TP-MSN@MnO₂ nanoparticle; (b) CEM cells pretreated with glutathione scavenger and then incubated with the TP-MSN@MnO₂ nanoparticle; (c) CEM cells pretreated with glutathione synthesis enhancer and incubated with the TP-MSN@MnO₂ nanoparticle. Reproduced with permission from [73]. Copyright 2014 American Chemical Society.

Figure 10

Schematic illustration of MSN probe-based intracellular detection of telomerase. Reproduced with permission from [76]. Copyright 2013 American Chemical Society. BHQ, black hole fluorescence quencher.