Fluorescent core-shell silica nanoparticles as tunable precursors: Towards encoding and multifunctional nano-probes

Article abstract of DOI:10.1039/b717038f

Core-shell silica nanoparticles comprised of a RuBpy doped silica core and a Pas-DTPA doped silica shell were synthesized and post-functionalized with an encoding fluorescence combination and multiplex imaging function. The Royal Society of Chemistry.

Full text of DOI:10.1039/b717038f

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Fluorescent core-shell silica nanoparticles as tunable precursors:
towards encoding and multifunctional nano-probes{{
Chuanliu Wu,a Jinqing Hong,a Xiangqun Guo,a Chaobiao Huang,b Jinping Lai,a Jinsheng Zheng,a
Jianbin Chen,a Xue Mua and Yibing Zhao*a
Received (in Cambridge, UK) 5th November 2007, Accepted 28th November 2007
First published as an Advance Article on the web 10th December 2007
DOI: 10.1039/b717038f
applications in nanostructural biological systems and multifunc-
tional bioimaging. Herein, we present a well-designed core-shell
silica nanoparticle as a tunable precursor towards encoding and
Core-shell silica nanoparticles comprised of a RuBpy doped
silica core and a Pas-DTPA doped silica shell were synthesized
and post-functionalized with an encoding fluorescence combi-
nation and multiplex imaging function.
multifunctional nano-probes.
A novel post-functionalization
strategy (Scheme 1) has been subsequently proposed to endow
this core-shell silica nanoparticle with an encoding fluorescence
combination and a multiplex imaging function.
Multiplex bioanalysis possesses several advantages over single-
target detection.1 Encoding silica nanoparticles prepared via
changing the type and concentration of the doped dyes are one
of the most common fluorescent nano-probes which have recently
been used for multiplex bioanalysis.1–3 However, the variation of
the type or concentration of the doped dyes can influence
the process of the preparation, and even probably leads to the
reduction of the homogeneousness and reproduction of the
prepared silica nanoparticles.3 Thus, the quest to prepare encoding
silica nano-probes with higher homogeneousness is of extreme
significance.
Core-shell silica nanoparticles which comprise of a tris (2,
29-bipyridyl) dichlororuthenium(II) (RuBpy) doped silica core and
a Pas-DTPA (Molecular structure is shown in Scheme 1) doped
silica shell were synthesized in two steps using a water-in-oil
microemulsion system.8 High resolution transmission electron
microscopy (TEM) was used for the characterization of the
preparation of core-shell architectural silica nanoparticles. Fig. 1a
shows an example of TEM images of RuBpy doped silica cores.
The diameter of the silica cores is 49 ¡ 3 nm. TEM images of the
ultimate core-shell architectural silica nanoparticles were shown in
Fig. 1b. The average diameter of the nanoparticles is 71 ¡ 4 nm.
HRTEM image shown in the inset of Fig. 1b and the particle size
distribution diagram shown in Fig. 1c both confirms the formation
of core-shell architecture. The Pas-DTPA doped silica shell
thickness is evaluated to be 11 nm.
In addition to the well-developed encoding silica nano-probes,
recently, multifunctional nano-materials have also become an
especially attractive research field.4–6 The development of multi-
functional nano-probes for MRI and subsequent fluorescence
imaging has been significant to the diagnosis of tumors and
surgical resection.5,6 Gadolinium doped fluorescent nanoparticles
have recently been explored as feasible nano-probes to satisfy this
urgent requirement.6 A silica matrix allows doping of a wide
variety of fluorescent dyes and gadolinium chelates, which make it
an ideal material for multifunctional bioimaging applications.6c–e
Explore the design and preparation methods of this type of
multifunctional nano-probes would be of great value to their
future applications.
Lanthanide ions exhibit low emission quantum yields because of
the very low absorption coefficients. For luminescent applications,
emission yields of lanthanide ions are typically enhanced by
combining with a chelate ligand.9 Many lanthanide chelate ligands
have been made, and Pas-DTPA used here shown in Scheme 1 is a
common chelate ligand for Tb3+ ions.9c Pas-DTPA contains two
parts: an organic chromophore (Pas) and a chelate (DTPA). The
chelate serves as a scaffold for attaching lanthanide ions in close
proximity to the organic chromophore (Pas). It is worth to note
that DTPA can combine quasi-irreversibly with lanthanide, such
as Tb3+ and Gd3+ ions.10 Thus, our core-shell silica nanoparticles
Recently, we have proposed a post-encoding concept to the
design and preparation of encoding fluorescent probes, which
makes the preparation process of multicolor fluorescent spheres
rather laborsaving and efficient.7 As a proof of this concept, a
hybrid silica-nanocrystal–organic dye superstructure (HSNOS) has
been successfully used as precursor for the preparation of
multicolor fluorescent spheres.7 However, it is not easy to fabricate
HSNOS with nano-scale and multifunctionality, which limits its
aDepartment of Chemistry and the Key Laboratory of Analytical
Sciences of the Ministry of Education, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen, Fujian, P.R. China.
E-mail: cooliu6@yahoo.com.cn; Fax: +86-592-2181637;
Tel: +86-592-2181637
bDepartment of Chemistry, Zhejiang Normal University, Jinhua,
Zhejiang, P. R. China
{ Electronic supplementary information (ESI) available: Details of
experimental section. See DOI: 10.1039/b717038f
Scheme 1 Schematic diagram showing the post-functionalization
{ The HTML version of this article has been enhanced with colour images
strategy.
750 | Chem. Commun., 2008, 750–752
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Fig. 1 (a) TEM images of RuBpy doped silica cores; (b) TEM images of
the ultimate core-shell architectural silica nanoparticles, inset: HRTEM
image; (c) The particle size distribution diagrams of RuBpy doped silica
cores and core-shell silica nanoparticles.
Fig. 2 (a) Normalized fluorometric excitation and emission spectra of
Pas-DTPA-Tb3+ (solid lines) and RuBpy (dot lines); (b) The normalized
fluorometric emission spectra of the core-shell silica nanoparticles before
(dot line) and after (solid line) incubating with Tb3+ ions, excitation
wavelength: 320 nm.
can be post-functionalized by incubating with different concentra-
tion of Tb3+ and/or Gd3+ ions. Fig. 2a shows the fluorometric
excitation and emission spectra of Pas-DTPA-Tb and RuBpy.
These two inorganic dyes share a broad overlapped excitation
spectrum but have two distinct maximum emission wavelengths,
with Pas-DTPA-Tb at 545 nm and RuBpy at 585 nm.
Fluorescence emission spectra of the core-shell silica nanoparticles
incubated with Tb3+ ions or not were shown in Fig. 2b. According
to the fluorometry studies of the post-functionalized silica
nanoparticles, and assuming the density of silica nanoparticles is
equal to pure silica,11 we have estimated that about 3500 Ru2+ ions
and maximum 2100 Tb3+ ions were capable to bind to each
nanoparticle. The emergence of fluorescence from Tb3+ ions is due
to the quasi-irreversible combination of Tb3+ with Pas-DTPA. The
porous silica matrix and unique core-shell nanoscale architecture
make the process of post-functionalization rather efficient.
To endow the core-shell silica nanoparticles with encoding
fluorescence combinations, the nanoparticles were incubated with
different concentration of Tb3+ ions. After approximately 10 h, the
incubated nanoparticles were separated by centrifuging. The
normalized fluorescence spectra taken from these post-functiona-
lized silica nanoparticles were shown in Fig. 3. As can be seen from
Fig. 3, a gradual increase in the fluorescence intensity of Tb3+ ions
was observed upon addition of increasing amounts of Tb3+ ions.
Fluorescence intensity ratio of the multiplex emission can be
accurately controlled by varying the amounts of the additive Tb3+
ions. The inset of Fig. 3 shows the correlation between the intensity
ratio at 545 nm to 590 nm and the relevant amounts of the additive
Tb3+ ions. To determine whether the intensity ratios have batch-
to-batch reproducibility, the average peak intensity ratios from five
parallel post-functionalized nanoparticle solutions were compared
Fig. 3 Fluorescence emission spectra of encoding silica nanoparticles
post-functionalized with Tb3+ ions; Inset: Correlation between the
intensity ratio and concentration of Tb3+ ions.
and the standard deviations for these intensity ratios are less than
3%. This high level of reproducibility allows not only more
intensity ratios to be distinguished but also higher precision in the
multiplex analysis.
To endow core-shell silica nanoparticles with both encoding
fluorescence combination and multiplex imaging function, silica
nanoparticles were post-functionalized via incubating with differ-
ent concentration ratios of Gd3+ and Tb3+ ions. As can be seen
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In summary, we have successfully developed a novel post-
functionalization strategy to fabricate encoding and multifunc-
tional silica nano-probes. Our post-functionalization strategy does
not involve the batch-to-batch preparation process or variation of
the type or concentration of doped dyes, which makes the
preparation process rather labor saving and efficient and leads to
well-controlled size homogeneousness. In addition, the core-shell
architectural silica nanoparticles will allow doping of other
fluorescent dyes and chelate ligands in the silica core and shell.
The post-functionalized nano-probes can also be used in time-
gated multiplex bioanalysis because of the long fluorescence
lifetime of the two inorganic dyes. It is expected that our post-
functionalized nano-probes will find various biological applica-
tions in multiplex bioanalysis, fluorescence imaging and MRI.
This research was supported by National Natural Science
Foundation of China (No. 20745004).
Fig. 4 Fluorescence emission spectra of encoding and multifunctional
silica nanoparticles post-functioned with different concentration ratios of
Tb3+ and Gd3+ ions; inset table: concentration ratios of Gd3+ and Tb3+
ions determined by ICP-MS.
Notes and references
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752 | Chem. Commun., 2008, 750–752
This journal is ß The Royal Society of Chemistry 2008