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Applications of Luminescent Silica Nanoparticles

Light is the most intuitive tool for people to recognize the world. Luminescent materials with special emission can be directly used in many ways such as lighting, display, and so on. At the same time, changes in fluorescence intensity can reflect some important information. Compared with separate luminescent dyes, LSNs have improved performances in applications, since silica provides a stable matrix for the luminescent dye. It provides an effective way for multifunction at the same time [6]. LSNs with multifunction and tunable surface have great application prospects and development potential in biology, lighting, and sensors.

Biolabeling and Medicine

LSNs have great application value in biology. Non-toxicity is a fundamental requirement for medical field, especially in vivo [78]. The fact that the common luminescent dyes are often toxic limits their clinical application [79]. Silica, a favorite non-toxic modified material, is a good solution to elimination of toxicity. Toxicity of silica nanoparticles (20–200 nm) were also carefully studied by In-Yong Kim et al. [80]. Size, dose, and cell type-dependent cytotoxicity were the issues in their research. Although high dose can cause a disproportionate decrease in cell viability, the silica nanospheres with 60 nm showed their good biocompatibility up to 10 μg/ml. Different cells had different tolerance to silica nanoparticles which indicated that it was necessary to have substantial tests before clinical tests. Although inhalation of silica particles can cause acute and chronic diseases including silicosis [81], silica still has potential in biological application at the nanoscale. The toxicity of luminescent silica nanoparticles to living cells was studied in detail by Yuhui Jin et al. [38]. From the DNA level to the cell level, the toxicity of RuBpy-doped LSNs were carefully tested. At a certain concentration, the results showed that the dye-doped luminescent silica nanoparticles were non-toxic to the targeted DNA and cells, which indicate that LSNs are a good solution to the non-toxic modification. Xiqi Zhang et al. [27] encapsulated AIE dye (An18, derivatized from 9, 10-distyrylanthracene with an alkoxyl endgroup) into the silica nanoparticles via a one-pot modified Stöber method. Coated with silica lead to an enhanced fluorescence intensity, good water solubility, and non-toxicity to living cells which made the An18-SiO₂ NPs had a potential for biomedical application.

LSNs have great application value in diagnosis and biolabeling. For hybrid imaging contrast agents, Dong Kee Yi et al. [48] combined magnetic particles (MPs) Fe₂ O₃ with QDs (CdSe) and encapsulated them in silica shell by reverse microemulsion method. The nanostructures of MPs with QDs are clearly showed in Fig. 14. Magnetic resonance imaging (MRI) is an effective method for disease detection, especially for cancer. The advantages of feasible usage, low cost, and accurate diagnosis make it more popular as a diagnostic tool [7]. The nanocomposites can be used as both optical and MRI contrast agents. It is worth mentioning that the presence of CdSe increased the effective magnetic anisotropy of the γ-Fe₂ O₃ -containg particles. This is a good attempt, but the low quantum yield (SiO₂ /MP-QD 1.1% to CdSe 11.4%) limits the actual effect. Willam J. Rieter et al. [39] also synthesized the same multifunctional nanocomposites. What is different is that [Ru (bpy)₃ ] Cl₂ was chosen as the luminescent core and the paramagnetic Gd complex was coated on the luminescent core by water-in-oil reverse microemulsion method. The nanocomposites were finally embedded in silica in the same way. The results of Fig. 15 proved that hybrid silica nanoparticles had good optical and MRI performances in biological imaging. Mesoporous silica nanospheres doped with europium (Eu-MSN) were obtained by Mengchao Shi et al. [32]. Nanoscale size (280–300 nm) and fluorescent property were the basic for an ideal biolabeling material. They found that Eu-MSNs had a positive influence on osteogenesis and angiogenesis-induction. By promoting proper response of macrophages and the expression of relevant genes, the defect of bone replaced by new bone and the healing process of skin wound can accelerate with Eu-MSNs. Besides the function of biolabeling, the LSNs showed the potential in tissue repair. LSNs can achieve the target binding effect by modifying the special group. In Duarte’s work [33], organosilane Bpy-Si was chosen as a ligand of Eu complex for the further reaction with silica. SiO₂ -[Eu (TTA)₃ (Bpy-Si)] nanoparticles were obtained with a uniform size (28 ± 2 nm). With a further modification of an amino acid spacer and an anchor group (anti-Escherichia coli , IgG1), the functionalized silica had the specific bonding with E . 대장균 박테리아. It was easy to get the distribution of E . 대장균 bacteria with luminescence. The bio-multifunction of LSNs was also carefully studied by Laranjeira et al. [82]. Gadolinium (Gd) composites with unique magnetic properties have potential in MRI contrast agents but Gd3+ ions are toxic in humans especially in kidneys and pancreas. GdOHCO₃ nanoparticles were chosen as the MRI contrast core and coated with silica layer via Stöber method. With the silica coating, the Gd composite (SiGdOHCO₃ ) had the same brightness of MRI contrast images but no degradation at designed pH values (5.5, 6.0, and 7.4). And SiGdOHCO₃ had little effect on human fibroblasts according to the cell proliferation assay which indicated an excellent biocompatibility. Silica provides a more stable environment and further possible modification for GdOHCO₃ without affecting MRI performance. By diverse micelles method, Atabaev et al. [83] synthesized Gd₂ O₃ :Tb ³⁺ ,Eu ³⁺ @SiO₂ nanoparticles which can be used as both MRI contrast and fluorescence agents in vivo. The above two examples perfectly reflected the role of LSNs in multifunction with the silica platform.

아 TEM image and b HRTEM image of SiO₂ /MP-QD nanoparticles [48]

The imaging results of monocyte cells with a optical microscopic, b laser scanning confocal fluorescence, c , d the images of monocyte cells with MR:left for unlabeled monocyte cells and right for hybrid silica nanoparticles labeled monocyte cells, e flow cytometric results of blank and hybrid silica nanoparticles-labeled monocyte cells, and f the cell viability with different amount of hybrid silica nanoparticles [39]

LSNs have great application value in drug delivery. Hongmin Chen synthesized luminescent mesoporous silica nanoparticles biofunctionalized by targeting motifs, which makes them applicable in drug delivery [47]. They first prepared APS-containing mesoporous silica particles, and subjected the products to calcination at 400 for 2 h. They synthesized mesoporous silica by the help of cetyltrimethyl ammonium bromide (CTAB). There were luminescent carbon dots in the silica matrix after calcination. The fluorescence intensity was at the maximum when the particles were excited at 380 nm. The target selectivity of FL-SiO₂ was achieved by surface modification of RGD peptide with the help of APS. They also studied the RGD-FL-SiO₂ loading and release of doxorubicin (Dox). After calcination, fluorescent mesoporous silica (FL-SiO₂ ) can still load Dox effectively. The porous structure was not affected by calcination. They found that RGD-FL-SiO₂ had good luminescent effect especially around the blood vessels of tumor in vivo imaging studies. 인테그린 α_v β₃ of the tumor was the key of the interactions. Although there are many excellent attempts to apply LSNs to medicine but less successful clinical tests in human beings means that there is still a long way to go for the real medicine applications.

Light-Emitting Devices

Due to their special emitting features, LSNs also play a vital role in light emission fields including the field emission- and liquid crystal-based display technologies [84]. WLEDs have received recent attention for their broad applications including general illumination and displays. Tunable color, high color purity, and luminescence efficiency are in line with the requirements of light-emitting diodes (LEDs) [85]. Quantum dot-based light-emitting diodes (QD-LEDs) have demonstrated recently, and may offer many advantages over conventional LED and organic light-emitting diodes (OLEDs) technologies in terms of color purity, stability, and production cost, while still achieving similar levels of efficiency. In order to improve the performances of polymer dots (Pdots) as WLED phosphors, Kaiwen Chang et al. [49] introduced some Pdots with different emission wavelength into the Stöber system to get encapsulated. The silica-encapsulated Pdots showed the same luminescence properties but markedly enhanced photostability.

To reduce the manufacturing complexity required for achieving full-color displays, it is more desirable to use a common device structure to achieve high efficiency for three primary colors (blue, green, and red). QDs have been widely used in display field because of its unique luminescent properties, such as high luminescent intensity, narrow emission spectra, and tunable emission. Chun Sun et al. [34] synthesized the perovskite QDs, CsPbBr₃ , as the light-emitting core of WLEDS. Only the perovskite QDs are not enough for a LED device since photostability and stability are necessary for an optical device under long-time work and elevated temperature. There are anion-exchange reactions between different halide QD nanoparticles which would widen the narrow emission spectrum. QD/silica composite were fabricated in APS to avoid oxidation and decomposition. So they used APTES as the QDs’ capping agent and improved the silica coating process to avoid the decomposition of the QDs. Green and red QD/silica composites were synthesized and a WLED was obtained by the combination of the composites with a blue LED chip. The WLED had good performances with great air stability as depicted in Fig. 16.

The optical performances of the WLED:a the emission spectra, b the CIE color coordinates and the color triangle of WLED (red dashed line) with the NTSC TV standard (black dashed line), c the power efficiency, and d emission spectra after working for a while [34]

LSNs can keep good dispersion, brightness, and photostability of QDs. Hung-Chia Wang et al. [35] provided a new composite method for QDs and silica (Fig. 17). By mixing the QDs with mesoporous silica powder of which pore size was bigger than that of QDs in non-polar solution, mesoporous silica green PQD nanocomposite was obtained after washing and drying. The quantum dot showed better thermal stability and photostability after composited with silica. On the other hand, QDs are a typical kind of aggregation-caused quenching (ACQ) nanoparticles, which means that it is necessary to keep a good dispersion to get a good brightness and photostability. Kai Jiang et al. [86] synthesized carbon dots with red, green, and blue luminescence with phenylenediamines as precursors to enhance luminescence properties as solution and poly (vinylalcohol) (PVA) film. But it would exist quenching effect as solid-state CDs which was fatal for LED devices owing to aggregation and the result Förster resonance energy transfer (FRET). To avoid the dispersion and the resulting FRET phenomenon, Junli Wang et al. [36] embedded carbon dots into silica matrix (Fig. 18) by dispersing carbon dots into the N -(3-(trimethoxysilyl)propyl) ethylenediamine (KH-792) and heating to form a homogenous CD/silica film. A white LED was fabricated by drying the CD/silica solution on the inner wall. By the assistant of silica, CDs were well dispersed with an appropriate distance without quenching which improve the performance as powders. Figure 18 showed the emission spectra and performance in WLED. And the CIE coordinates (0.44, 0.42) and correlated color temperature (CCT) (2951 K) suggested that it was suitable for indoor illumination.

아 The formation progress of MP-CsPbBr3PQDs. ㄴ The luminescence intensity and the color triangle of WLED [35]

The performance of WLED showed as a the emission spectrum and b for CIE chromaticity and CCT [36]

Sensors

Luminescent silica showed the excellent performances on static luminescent materials, such as biolabeling and WLED phosphors. All these were based on their unique and stable optical properties. When it came to dynamic luminescent materials, LSNs also display the same wonder [9]. The luminescent sensors of pH [28], ions [87], and temperature [40] are following as representatives.

pH value have great influence on the luminescence intensity which inspires luminescent pH sensor. In the same principle as ref. [22], Atabaev et al. synthesized the same ratiometric pH sensor [28]. FITC was chosen as the pH-dependent luminescence dye and Y₂ O₃ :Eu ³⁺ as pH stable dye. With the Stöber coating of silica, Y₂ O₃ :Eu ³⁺ @SiO₂ with FITC composite NPs were successfully synthesized. The change of pH was reflected by the ratio of fluorescence intensity (I _FITC /나 _Y2O3:Eu3+ ). The standard dye led to a less influence of concentration and a more accurate result.

LSNs can also be used as ions sensors. Based on the changes of luminescence intensity with the measured physical quantity, LSNs have been applied to many sensor fields by the environment-dependent effect of the luminescence. Quenching effect is an effective detective tool to detect the changes of quenching factors such as ions and pH value with external quenching mechanisms such as FRET and photoinduced electron-transfer (PET) [9]. Sensors for metal ions are important fields whether in cells or open system. Won Cho et al. [37] synthesized europium (III) coordination polymer (EuCP) and found the specific quenching effect of Cu ²⁺ (Fig. 19). In view of this fact, they synthesized silica@EuCP microsphere which have the same sensitivity on Cu ²⁺ with less mass of europium. As an auxiliary material, silica can effectively reduce the amount of sensor materials. Both of them have their unique situations. Besides quenching effect, there are some different effects which can be used in the fields of sensors. 2,2-Dipicolylamine (DPA) and its derivatives have good affinity to heavy ions. And enhanced luminescence effect would happen after chelated with heavy ions. Yu Ding et al. [29] modified silica spheres with N ,N ′-bis (pyridine-2-ylmethyl)ethane-1,2-diamine (Fig. 20). The concentration of heavy ions (Cd ²⁺ Hg ²⁺ 및 Pb ²⁺ ) in samples can be determined by the change of fluorescence intensity. The test in real water samples and simulated biological samples confirmed the heavy metal ions-binding ability and the detection which has application prospects in the water monitoring and so on.

아 Confocal microscopy and OM (inset) images of silica@EuCP microspheres. ㄴ Luminescence spectra with different Cu (NO₃ )₂ in MeCN; luminescence intensity changes (c ) and photograph (d ) with different metal ion solutions (5 mM) [37]

The formation and sensing progress scheme of sensitive fluorescent sensor (FSCHP) [29]

Temperature sensors are also important applications of LSNs. Temperature is a basic variable in most science fields. The temperature dependence of radiative and non-radiative transition rates is the core content of temperature sensing which makes it possible for luminescence temperature sensing, with the contactless and large-scale advantages [9]. However, in order to be applied in practice, their stability is crucial as the environment of application is more complex than of that of experiment condition. Silica is an ideal matrix to improve their performance for application. Mirenda et al. [40] synthesized silica as the core and then TEOS was hydrolyzed with Ru (bpy)₃ Cl₂ to form the Ru (bpy)₃ @SiO₂ NP. The emission spectra of Ru (bpy)₃ @SiO₂ NPs (Fig. 21) showed that the intensity of Ru (bpy)₃ @SiO₂ NPs decreased linearly as the temperature rising as the result of the activated non-radiative ³ d-d state (20–60 °C, λ_exc  = 463 nm). The polyethyleneimine (PEI)-modified glass with Ru (bpy)₃ @SiO₂ NPs showed the same trend as the NPs which proved that the potential as the temperature sensing. With cycling the temperature between 20 and 60 °C, the relative slope decreased until the seventh cycle which meant that it is necessary to condition to obtain the stable sensing materials. The influence of temperature on probes is complicated. So it is necessary to research the temperature-dependent luminescence of the probes to know how to apply it into temperature sensors. Temperature is a fundamental variable that governs diverse intracellular chemical and physical interactions in the life cycle of biological cells. The change of temperature reflects the level of cell metabolism. GdVO₄ co-doped with Er ³⁺ (1 mol%) and Yb ³⁺ (1 mol%) has the potential to apply as the temperature sensor. To improve their performance as temperature sensor, Savchuk et al. [41] coated silica shell on the nanoparticles surface by Stöber method. The fluorescence intensity ratio (FIR) of Er, Yb:GdVO₄ , 나 ₅₂₀ /나 ₅₅₀ , had a certain linear relationship with temperature in the range from 297 to 343 K after excitation at 980 nm. And the probes got enhanced thermal sensitivity, high thermal resolution and good stability in different solvents. And the result of the ex vivo experiment to monitor temperature evolution with the special sensor showed in Fig. 22 proved that Er, Yb:GdVO₄ @SiO₂ core-shell nanoparticles had a good thermal resolution as the temperature sensor in biomedical applications.

아 PL spectra of Ru (bpy)₃ @SiO₂ under different temperature. ㄴ The peak intensity changes as a function of temperature [40]

아 나 ₅₂₀ /나 ₅₅₀ with different temperature for Er, Yb:GdVO₄ and Er, Yb:GdVO₄ @SiO₂ . ㄴ The sketch map for the ex vivo temperature determination experiment. ㄷ The results of the temporal evolution of temperature for the Er, Yb:GdVO₄ @SiO₂ and a thermoresistor Pt-100 [41]