Open Access
Add to BibSonomyAbstract
High quality near-infrared (NIR) persistent luminescence nanospheres (PLNPs) were synthesized using a simple mesoporous template method. The as-synthesized NIR persistent luminescence nanoparticles have uniform spherical morphology, tunable sizes, and a nominal composition of SiO2/CaMgSi2O6:Eu2+, Pr3+, Mn2+ (denoted as SEPM). Their NIR persistent luminescence at 660 nm can be detected during more than 1 hour. The in vivo distribution of the nanoparticles in the abdomen can be detected in real time after injection into the abdomen of a mouse. The nanoparticles can be metabolized from the lymph circulation and transferred from the abdomen to the bladder. The results indicate an effective method to offer high quality NIR persistent luminescence nanoprobes for imaging.
© 2014 Optical Society of America
1. Introduction
Due to the continuous growing demands for imaging tools for biomedical applications, optical imaging has become a powerful tool for biomedical applications [1–3]. Because of the photo-bleaching effect of traditional organic fluorophores, a lot of inorganic luminescent probes have been explored extensively, such as semiconductor nanocrystals [4], upconversion nanocrystals [3] and carbon nanomaterials [5, 6], etc. However, the nowadays available optical probes are still far from satisfying the keep-growing demand for various imaging modalities. Novel kinds of optical imaging probes are still needed.
Persistent luminescence nanoparticles (PLNPs) are a new group of optical nanoprobes which can be used in luminescent imaging of live animals [7–9]. The persistent luminescence (also known as long-lasting phosphorescence, afterglow, etc.) of the reported near-infrared (NIR) PLNPs could last several hours after optically excited in vitro [8]. And their in vivo distribution allowed real-time detection after the injection without the need for any external simultaneous excitation light source. Due to the removal of the background noise originating from in situ excitation, the signal-to-noise ratio could be significantly improved. Moreover, an up-to-date report has extended the persistent luminescence time from several hours to more than a week [10]. These unique optical properties of PLNPs have shed a new light on traditional persistent luminescence materials for biological applications and will surely facilitate the rapid development of optical imaging. However, reports of applications of PLNPs in bioimaging and bioanalysis have been rare to date. Although many methods have been developed to prepare persistent luminescence materials, such as solid state reaction method [10],sol-gel process [7], combustion method [11], microwave assisted method [12], and spray pyrolysis method [13], the resulting particles were usually in micrometer scale, highly agglomerated and irregular in morphology, which undoubtedly would hinder their further applications for in vivo imaging. Nowadays, a gravity separation method has to be employed to isolate the smallest nanoparticles from bulk materials prepared by sol-gel method, which suffered severely from trivial, time-consuming procedures and very small yields [9, 14].
CaMgSi2O6:Eu, Pr, Mn, having a diopside crystal structure, is one of the promising NIR persistent luminescence materials reported recently by Maldiney and associates, which have been successfully applied in in vivo imaging of mouse [8]. However, there are little reports about the synthesis of diopside nanoparticles with controllable sizes and morphologies in a simple and efficient way and in large scale, which is very important to generalize their applications in biology and medicine. Template method is a facile and effective method in the synthesis of nanomaterials with highly controllable sizes and morphologies [15, 16]. Mesoporous silica nanospheres (MSNs) can be synthesized conveniently with tunable sizes and morphologies and have become one of the most important hard templates in the synthesis of various useful materials. Although, MSNs has found applications as templates on the synthesis of various materials, such as noble metals [17], metal oxides [18], carbon materials [19], phosphors [20], etc, reports are rare on the synthesis of persistent luminescence materials using mesoporous silica as templates. Inspired by the wide application of MSNs as templates, we have recently developed a convenient template method to synthesize blue PLNPs both with narrow size distributions and in large scale [21]. In order to decrease the light absorption and scattering, the afterglow spectrum of PLNPs should be located in the so-called NIR optical imaging window (600 ~1000 nm) [22]. In this paper, hybrid NIR PLNPs with a nominal composition of SiO2/ CaMgSi2O6:Eu0.01, Pr0.02, Mn0.10 (SEPM) [were finally synthesized by this facile template method. Furthermore, we tried to investigate the abilities of the surface modified nanoparticles to be metabolized via the lymph circulation using persistent luminescence imaging in vivo, which is as important as the blood circulation system.
2. Experimental
2.1. Synthesis of MSNs
MSNs were synthesized according to a recently reported method with modifications [23]. In a typical procedure, 0.2 g of cetyltrimethylammonium bromide (CTAB), 25 ml of water, calculated amount of ethanol, 50 μL of diethanolamine were mixed together and stirred in water bath of 60 °C for 30 min. Then 2 mL of tetraethoxysilane was added into the solution rapidly and stirred for 2 hr. Finally, the solution was cooled to room temperature and MSNs were centrifuged after 20 mL acetone was added to the as-synthesized mixture. The precipitate was heated at 550 °C for 2 hr to remove CTAB templates.
2.2. Synthesis of NIR PLNPs
NIR PLNPs, SEPM, were synthesized according to our previously reported method with modifications [20]. Briefly, mixed nitrate solution of Ca2+, Mg2+, Eu3+, Pr3+, Mn2+ was prepared by dissolving their corresponding nitrates with the final concentration 1.0 M, 1.0 M, 0.010 M, 0.020 M, 0.10 M, respectively. 1.0 g of the as-synthesized MSNs was mixed with 20 mL of the as-prepared nitrate solution and was stirred for 24 hr. Then the ionic impregnated MSNs were centrifuged and dried at 80 °C for 5 hr. The dried precursor was firstly pre-annealed at 800 °C for 2 hours at a heating rate of 1 °C per min. The pre-annealed product was grinded using a motor and pestle. NIR SEPM nanoparticles were finally formed after being annealed at certain temperatures for 5 min at a heating rate of 10 °C per min. Both of the heating procedures were carried out at a weak reducing atmosphere (10%, H2/Ar). The samples, using MSNs-150 as templates, synthesized at 1000 °C, 1100 °C, and 1200 °C are denoted as SEPM-1000, SEPM-1100, and SEPM-1200, respectively. The key point of this method is based on the use of MSNs both as silicon source to form CaMgSi2O6 diopside phase and hard templates to control the morphologies of the resulting SEPM nanoparticles.
2.3. Surface functionalization
Because of the high synthesis temperature, the as-synthesized SEPM nanoparticles are lack of active groups to be grafted with functional biological molecules. We use the widespread Stöber method to obtain amino-group modified nanoparticles. Briefly, 100 mg of SEPM nanoparticles synthesized at 1000 °C were dispersed into 100 mL of 4.2% concentrated ammonia/ethanol (v/v) solution assisted by ultrasound for 30 min. 5 μL of tetrathoxysilane and 5 μL of 3-aminopropyltriehoxysilane were added in sequence under ice/water bath situation. The mixture was stirred for 24 hours to ensure the complete hydrolysis of silicane. Amino-group modified SEPM nanoparticles were obtained by centrifugation and dispersed into 100 mL of ethanol. 100 μL of oleic acid, 40 mg of N-(3-dimethyaminopropyl)-N’ethylcarbodiimade hydrochloride (EDC), 60 mg of N- hydroxysuccinimide (NHS) were added and stirred for 24 hours at room temperature to generate oleic acid modified hydrophobic SEPM nanoparticles. The hydrophobic nanoparticles were purified by centrifugation and washing with ethanol for three times. Hydrophilic Tween20-modified SEPM (SEPM-Tween20) nanoparticles were obtained by dispersing these hydrophobic nanoparticles into 100 mL of physiological saline containing 0.1% Tween20 assisted by ultrasound.
2.4. Cell viability test
The cytotoxicity was measured using 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT, SIGMA, USA) assay. The human umbilical vein endothelial cells (HUVE cells, ATCC, CRL-1730) were grown in 96 well plates (CORNING, USA) overnight. When the cells were approximately 70-80% confluent, serial dilutions of SEPM-Tween20 were added and incubated for 24 h at CO2 incubator (Thermo heracell 150i, USA). Then 20 µL of MTT was added to each well and incubated for 4 h at 37 °C and 5% CO2. Then the medium was removed, and dimethyl sulphoxide (DMSO, SIGMA, USA) was added to dissolve the formazan. After 20 min, the absorbance of formazan was measured at 490 nm using a microplate reader (Molecular Devices, Sunnyvale, CA, USA), with a reference at 650 nm.
2.5. Imaging in vivo
SEPM-Tween20 nanoparticles (200 μL, 1 mg/mL) were injected into the abdomen of a live mouse after irradiated by a UV lamp (365 nm) for 10 min. After 1 min of the injection, the persistent luminescence signals were acquired for 60 s at fixed time intervals using a small animal imaging in vivo system (Caliper life science, IVIS lumina II). The imaging setup is as follows: binning 8, f/stop 1, exposure 60 s, interval 5 min, excitation closed and emission block open.
2.6. Characterization
The X-ray powder diffraction (XRD) was performed on Panalytical X’pert PRO diffractometer equipped with Cu Kα radiation (λ = 1.5418 Å). The morphology of the samples was inspected using field emission scanning electron microscopy (FESEM, HITACHI, S-4800) and a transmission electron microscopy (TEM, HITACHI, H-7650) at accelerating voltages of 5 kv and 100 kv, respectively. Energy-dispersive X-ray spectroscopy (EDS) was obtained on FESEM at an accelerating voltage of 30 kv. The luminescence spectra and time decay curves were measured using a NIR fluorescence spectrometer (Edinburgh, FLS920). The surface charge of the nanoparticles in Tris-HCl buffer and the hydrodynamic size distribution were measured using a Zetasizer (Malvern, 3000HS). The infrared spectra were conducted on a Fourier transform infrared spectroscopy (FTIR, Nicolet AVATAR, FT-IR360).
3. Results and discussion
3.1. Phase formation of diopside in MSNs
MSNs have poor thermal stability when the temperature is higher than 900 °C. In order to retain the original uniform spherical morphology of the MSNs, a very short annealing time (5 min) was chosen during the annealing procedure. The crystalline structures of the SEPM nanoparticles are confirmed by XRD analysis (Fig. 1). The XRD patterns of the samples indicate that the diopside phase start to appear at a temperature as low as 1000 °C, although the annealing time is very short. Nearly all of the peaks can be attributed to diopside CaMgSi2O6 phase, confirming the formation of monoclinic diopside (JCPDS no. 01-078-1390). The doping of Eu(II), Pr(III) and Mn(II) ions has no significant effect on the global structure of the final product. The weak diffraction peaks of the samples synthesized at 1100 °C and 1200 °C at 20.86 o and 26.66 o can be attributed to the formation of quartz phase of silica (JCPDS no. 00-005-0490), which is due to the crystallization of the excess amount of amorphous silica supplied by the MSNs templates. A new strong diffraction peak at 21.94 o can be observed from the sample synthesized at 1200 °C, which can be assigned to the formation of cristobalite phase of silica (JCPDS no. 01-077-1317).
3.2. Morphologies of the as-synthesized SEPM
The regular morphology of the as-synthesized MSNs is shown in Fig. 2(a). The MSNs templates have highly regular spherical morphology with a very narrow size distribution. The large pore volume of MSNs can be used to absorb alkaline earth ions and rare earth ions which consist of the final NIR persistent luminescence material. After calcination at 1000 °C for 5 min, these nanoparticles still keep their original spherical morphology and free-standing nature. The smooth surfaces of the MSNs templates become coarser and a little shrink in particle diameter can also be observed after the formation of SEPM, as shown in Fig. 2(b). Such SEPM nanoparticles possess suitable sizes, regular spherical morphology and thus can avoid the laborious separation process. Usually, higher temperatures leads to higher persistent luminescence intensities, while the morphologies of the as-synthesized persistent luminescence nanoparticles depend severely on the calcination temperature and time. When the temperature increases to 1100 °C, only a part of the nanoparticles can survive the annealing procedure (Fig. 2(c)). And nearly all the nanoparticles have disappeared at 1200 °C (Fig. 2(d)). The atomic ratio of the sample, SEPM-1000, was detected using EDS analysis. The result indicates that the rough atomic ratio of Ca: Mg: Si is ca. 1.0: 1.2: 9.1, as shown in Fig. 2(e). The content of silicon is highly excessive than that is needed to form CaMgSi2O6 matrix. The excess amount of silicon may have important effect on the controllable sizes and morphologies of the final SEPM-1000 sample. The TEM image of SEPM-1000 is shown in Fig. 2(f). The as-synthesized nanoparticles seem like golf balls with uniform nano-spots doped inside the nanoparticles. The nano-spots may be the as-synthesized ultrasmall crystalline grains of diopside. The nanoparticles have regular spherical morphology with a very narrow size distribution. The particles can be dispersed easily and only slight soft agglomeration can be seen.
Fig. 2 FE-SEM images of the as-synthesized MSNs-150 (A), SEPM-1000 (B), SEPM-1100 (C), SEPM-1200 (D), EDS analysis (E) and TEM (F) of SEPM-1000.
The deformation of the nanoparticles at higher temperatures may be caused by the crystallization between the adjacent amorphous silica templates during the high temperature annealing procedure. The ion-impregnated SEPM precursor can be formed by immersing the MSNs templates in the ionic solution and careful pre-annealing to 800 °C. After being annealed to 1000 °C, the impregnated ions can react with the highly active amorphous silica templates to form diopside CaMgSi2O6 phase. The as-synthesized diopside crystalline grains are separated from each other by the silica templates and cannot grow up to form bigger particles. Because the annealing time is very short, the excess amount of silica is still mainly amorphous and free-standing nanoparticles can be formed. When the annealing temperature increases to 1100 °C, the amorphous silica becomes to be converted to quartz silica phase and the adjacent silica nanoparticles start to fuse together to form big particles. When the annealing temperature increases further to 1200 °C, quartz silica phase starts to be converted to cristobalite phase and the adjacent big quartz silica particles start to form bigger cristobalite grains. The annealing procedure have crucial effects on the sizes and morphologies of the final products. In conclusion, the template method uses pre-synthesized templates with good chemical stabilities. The ionic impregnation procedure has little effect on the morphologies of the final product which are mainly dependent on the ones of the templates. These properties of the template method can ensure good controllability and repeatability.
3.3. Optical properties
The CaMgSi2O6:Eu, Mn, Pr synthesized by Maldiney using sol-gel method has two emission peaks at around 580 nm and 685 nm (excitation 350 nm) [8]. Different from their result, the emission spectrum of the as-synthesized SEPM nanoparticles are composed of three emission peaks at ca. 450 nm, 577 nm and 685 nm (excitation 350 nm), as shown in Fig. 3(a). The emission peak at ca. 450 nm can be attributed to the typical 4f65d1-4f7 transition of Eu2+. The bands at 577 nm and 685 nm are similar to those observed for diopsides doped only with Mn2+ and correspond to the same 4T1-6A1 transition of Mn2+ in two different substituted crystal lattices (Ca2+and Mg2+) [24]. Mn2+ in the Mg2+ site is responsible for the emission peak at ca.685 nm, whereas Mn2+ in the Ca2+ site leads to the emission at ca.577 nm.
Fig. 3 Luminescence properties of the SEPM samples: (A) photoluminescence emission spectra (excitation, 350 nm), (B) the influence of doping concentration of Mn2+ on the luminescence intensity at 450 nm and 685 nm, (C) persistent emission spectrum after pre-illumination by a 365 nm UV lamp for 10 min and (D) decay curve of SEPM-1000 monitored at 660 nm.
In order to confirm the successful energy transfer from Eu2+ to Mn2+ in our hybrid SEPM system, an univariate analysis of the doping concentration of Mn2+ was performed (Fig. 3(b)). The emission intensities of Eu2+ decrease rapidly while the emission of Mn2+ at ca. 685 nm increases when the concentration of Mn2+ increases from 0.02 to 0.10, which indicate the successful energy transfer procedure. Due to the concentration quenching effect, the emission intensity from Mn2+ starts to decrease when the concentration of Mn2+ increases further from 0.10 to 0.14. In order to ensure intense NIR emission, the molar ratio of Mn2+ is fixed to 0.10 versus the amount of Mg2+.
In order to detect the persistent luminescence spectrum of SEPM1000, the sample was pre-illuminated by a 365 nm UV lamp for 10 min. After turning off the UV lamp for 5 min, the persistent luminescence spectrum was detected using a NIR spectroscopy. The persistent luminescence spectrum of SEPM1000 exhibits two peaks at ca. 484 nm (from Eu2+) and 660 nm (from Mn2+), as shown in Fig. 3(c). The persistent luminescence at 484 nm can be assigned to the emission of Eu2+. The afterglow emission peak centered at 660 nm can be attributed to the emission of Mn2+ due to the energy transfer from Eu2+. The deep red to NIR afterglow emission is located in the NIR optical imaging window, which can be applied in the field of imaging in vivo. The NIR afterglow emission of SEPM is able to be tested during more than 60 min (Fig. 3(d)) after irradiated by a UV lamp (365 nm) for 10 min. The Digital images of the as-synthesized SEPM-1000 in daylight, phosphorescent images in dark with and without a 550 nm longpass filter were acquired using a SLR camera (Nikon D7000) and shown in the inset of Fig. 3(d).
3.4. Surface modification and cell biocompatibility
The applications of these nanoparticles in imaging usually need to endow them water-dispersibility. Thus, hydrophilic surface modification has to be performed. The modification process is shown in Fig. 4(a). Because of the high synthesis temperature, the annealed SEPM nanoparticles are lack of active groups. Amino groups were firstly grafted to the surface of the nanoparticles via the widely used Stöber method. Oleic acid was anchored onto the particle surface by the condensation reaction between the amino and carboxyl groups catalyzed by EDC-NHS system. A hydrophilic surfactant, tween20, is self-assembled onto the hydrophobic oleic acid terminated surface to form hydrophilic nanoparticles. The successful modification is certified by FTIR spectra (Fig. 4(b)). The FTIR spectrum of SEPM is a typical inorganic one and no absorption peaks between 2500 to 4000 cm−1 can be seen. After the functionaliztion of amino group, an apparent absorption peak appears at ca. 3445 cm−1 in the FTIR spectrum of SEPM-NH2, which can be attributed to the stretching vibration of N-H bond. After the reaction between SEPM-NH2 and oleic acid, a characterized peak of carbonyl group appears at 1630 cm−1. The strong peak at ca. 3423 cm−1 may be attributed to the stretching vibration of the N-H bond of the amide group and the O-H bond of the carboxyl group of residual oleic acid. Tween 20 is an is a polyoxyethylene derivative of sorbitan monolaurate. It has a long polyoxyethylene chain (-CH2-, C-O-C) and a short fatty acid ester moiety (CH2, CH3), approximately 110 C-H bonds, 25 C-O-C bonds, and only one C = O bond. Because the amount of C = O is relatively small and the oleic acid modified samples also have carboxyl group, we can only certify the existence of tween20 from the IR absorption of C-O-C and the increased absortion of CH2. After the self-assembly of Tween20 on the hydrophobic surface of the nanoparticles, a weak peak of C-O-C stretching vibration appears at ca. 1352 cm−1, which may come from the hydrophilic polyethylene glycol chain of Tween20. The strong dual peaks at 2917 cm−1 and 2876 cm−1 can be assigned to the C-H stretching vibration of the methane group of Tween20. After the hydrophilic modification, the as-synthesized nanoparticles, denoted as SEPM-Tween20, has a relative narrow size distribution with a hydrodynamic diameter of ca. 170 nm and a slight negative zeta-potential of ca. −17 mV, as shown in Fig. 4(c) and Fig. 4(d), respectively.
Fig. 4 Scheme of the hydrophilic modification process (A), FTIR spectra (B), hydrodynamic size distribution (C) and zeta potential (D) of SEPM-Tween20.
Bulk or micrometer CaMgSi2O6 (diopside) has become a hot topic of research for bone tissue repair applications and exhibits excellent biocompatibilities [25]. However, the nanoparticles might have different biological performances. Thus, a cell viability test was carried out to confirm the biocompatibility of both the as-synthesized SEPM and SEPM-Tween20 nanoparticles. HUVE cells were treated with various concentrations of SEPM and SEPM-Tween20 nanoparticles for 24 h to determine the influence of concentration of the nanoparticles. The viability of the non-treated cells is assumed to be 100%. The results indicate that both the SEPM and the SEPM-Tween20 nanoparticles exhibit excellent cell biocompatibility and no apparent toxic effect on the tested cells can be observed, even if the concentration of the nanoparticles is increased to 50 mg/L, as shown in Fig. 5. The dosage of the nanoparticles used in the cell test is much higher than that used in the imaging experiments (ca. 6 mg kg−1).
Fig. 5 Cell viability of HUVE cells after 24 h exposure to increasing doses of SEPM and SEPM-Tween20 by the MTT assay. Control cells were cultured in nanoparticle-free media. Results are expressed as mean ± SD of three independent experiments.
3.5. Application in imaging in vivo
NIR persistent luminescence nanoparticles, synthesized using sol-gel method and a gravity seperation process, have been used in animal imaging, and proved to be able to circulate from the blood circulation successfully [9]. However, to the best of our knowledge, little work has been done on the metablic capability of NIR persitent luminescence nanoprobes from the lymph circulation, which is as important as the blood circulation system. In order to investigate the transfer process of the nanoprobes via the lymph system in real time, 200 μL of the as-synthesized SEPM-Tween20 nanoparticles (ca. 1 mg/mL) was injected into the abdomen of a mouse after irradiated by a UV lamp (365 nm) for 10 min. The phosphorescent signals were acquired for 60 seconds at every 5 min interval during 1 hr using a small animal imaging in vivo system equipped with a CCD camera. Due to the no need of constant probe illumination during signal acquisition, the background signal originating from the autofluorescence of tissue organic components can be effectively eliminated. Furthermore, the tissue scattering and absorption can be minimized by adjusting the luminescence spectrum into the NIR imaging window. It should be noted that the persistent luminescence at ~484 nm might cause in situ autofluorescence. But, this problem might be not very serious due to the relative much weaker intensity and poorer penetration ability of the peak at ~484 nm comparing with the one at ~660 nm. The results show that the afterglow signals are very strong and are enough to track the real-time distribution of SEPM nanoparticles even after 1 hour of injection (Fig. 6). Interestingly, an apparent transfer of the persistent luminescence nanoparticles from the injection site to the bladder can be clearly seen. The capability of the nanoprobes to transfer via the lymph system indicates that the persistent luminescence nanoprobes might found potential applications in lymph imaging, which is important in drug delivery and tumor imaging.
Fig. 6 Luminescence images of the real-time distribution of the as-synthesized SEPM-Tween20 nanoparticles in the abdomen of a mouse after 1 min (A), 1 min, (B) 20 min, (C) 40 min, (D) 60 min of the injection.
In order to quantification of the real time distribution, 4 areas were selected to detect the ROI of the injection site (area 1), the spleen (area 2), the kidney (area 3), and the bladder (area 4) using the software of the imaging system, as shown in the inset of Fig. 6. The ROI ratio of ROI 2/ROI 1, ROI 3/ROI 1, and ROI 4/ROI 1 are used to measure the transfer degree of the nanoparticles. The results indicate that all the ROI ratios from the spleen, the kidney, and the bladder increase along with the time after the injection and the ROI ratios increase from the spleen to the kidney, and then to the bladder, as shown in Fig. 7. These results indicate a possible metabolic pathway of the injected nanoparticles, in which the nanoparticles are firstly collected by the spleen from the lymph system, then transferred quickly to the kidney, and finally accumulated at the bladder. The successful metabolism of the nanoparticles from the lymph circulation can avoid the filtering of liver in the case of vain injection and may endow them potential applications in imaging of lymph nodes and help to find the metastatic tumor transferring from the lymph system. These results indicate that the as-synthesized NIR persistent luminescence nanoparticles might find their potential applications as novel noninvasive optical nanoprobes trackable in live animals and in optical imaging of tissue, organ, or tumor. It should be noted that all the mice used for imaging have survived the experiment and their shaved hair can grow up again in approximate two weeks. This kind of persistent luminescence material can endow long time in vivo observation without the need to kill the model animals, which will decrease both of the number and the individual difference of the model animals.
4. Conclusion
NIR PLNPs can be obtained with highly controllable morphologies and sizes in large scale by using MSNs as mesoporous templates. The templates can retain their uniform morphologies after calcination at 1000 °C. The as-synthesized nanoprobes a composite of diopside CaMgSi2O6 phase and silica phase. Their sizes and morphologies are mainly dependent on the ones of the templates. The annealing procedure is the main factor that affects the morphologies of the product, while the procedure in the solution has little effect. These properties of the template method can endow it with good controllability and repeatability and batch production. After hydrophilic modification, nanoprobes exhibit good biocompatibility. The NIR afterglow emission of the as-prepared SEPM nanospheres can be used to track the real time bio-distribution in vivo with good signal-to-noise ratio. The nanoparticles can be metabolized from the lymph circulation and transferred from the abdomen to the bladder. Such novel NIR persistent luminescence nanospheres have potential applications as novel persistent luminescence nanomarkers, nanoprobes, drug carriers, etc. Furthermore, this template method can be easily transplanted to the synthesis of other kinds of PLNPs.
Acknowledgments
This work was supported by the “One Hundred Talents” Program of CAS (Grant No.09i4281c10), National Key Technology Support Program (2012BAC25B04), National High-Tech R&D Program of China (863 Program, 2012AA062607), and Science and Technology Project in Xiamen (3502Z20132012).
References and links
1. J. A. Barreto, W. O’Malley, M. Kubeil, B. Graham, H. Stephan, and L. Spiccia, “Nanomaterials: applications in cancer imaging and therapy,” Adv. Mater. 23(12), H18–H40 (2011). [CrossRef] [PubMed]
2. S. Luo, E. Zhang, Y. Su, T. Cheng, and C. Shi, “A review of NIR dyes in cancer targeting and imaging,” Biomaterials 32(29), 7127–7138 (2011). [CrossRef] [PubMed]
3. J. Zhou, Z. Liu, and F. Li, “Upconversion nanophosphors for small-animal imaging,” Chem. Soc. Rev. 41(3), 1323–1349 (2012). [CrossRef] [PubMed]
4. R. G. Aswathy, Y. Yoshida, T. Maekawa, and D. S. Kumar, “Near-infrared quantum dots for deep tissue imaging,” Anal. Bioanal. Chem. 397(4), 1417–1435 (2010). [CrossRef] [PubMed]
5. Z. Liu, K. Yang, and S. T. Lee, “Single-walled carbon nanotubes in biomedical imaging,” J. Mater. Chem. 21(3), 586–598 (2011). [CrossRef]
6. K. Welsher, S. P. Sherlock, and H. Dai, “Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window,” Proc. Natl. Acad. Sci. U. S. A. 108(22), 8943–8948 (2011). [CrossRef] [PubMed]
7. Q. le Masne de Chermont, C. Chanéac, J. Seguin, F. Pellé, S. Maîtrejean, J. P. Jolivet, D. Gourier, M. Bessodes, and D. Scherman, “Nanoprobes with near-infrared persistent luminescence for in vivo imaging,” Proc. Natl. Acad. Sci. U. S. A. 104(22), 9266–9271 (2007). [CrossRef] [PubMed]
8. T. Maldiney, A. Lecointre, B. Viana, A. Bessière, M. Bessodes, D. Gourier, C. Richard, and D. Scherman, “Controlling electron trap depth to enhance optical properties of persistent luminescence nanoparticles for in vivo imaging,” J. Am. Chem. Soc. 133(30), 11810–11815 (2011). [CrossRef] [PubMed]
9. T. Maldiney, C. Richard, J. Seguin, N. Wattier, M. Bessodes, and D. Scherman, “Effect of core diameter, surface coating, and PEG chain length on the biodistribution of persistent luminescence nanoparticles in mice,” ACS Nano 5(2), 854–862 (2011). [CrossRef] [PubMed]
10. Z. W. Pan, Y. Y. Lu, and F. Liu, “Sunlight-activated long-persistent luminescence in the near-infrared from Cr3+-doped zinc gallogermanates,” Nat. Mater. 11(1), 58–63 (2012). [CrossRef] [PubMed]
11. Q. Yang, Y. L. Liu, C. X. Yu, G. X. Zhu, L. Sha, Y. H. Yang, M. T. Zheng, and B. F. Lei, “Rapid combustion method for surface modification of strontium aluminate phosphors with high water resistance,” Appl. Surf. Sci. 258(18), 6814–6818 (2012). [CrossRef]
12. F. L. Sun and J. W. Zhao, “Blue-green BaAl2O4:Eu2+,Dy3+ phosphors synthesized via combustion synthesis method assisted by microwave irradiation,” J. Rare Earths 29(4), 326–329 (2011). [CrossRef]
13. W. Y. Teoh, R. Amal, and L. Mädler, “Flame spray pyrolysis: An enabling technology for nanoparticles design and fabrication,” Nanoscale 2(8), 1324–1347 (2010). [CrossRef] [PubMed]
14. T. Maldiney, M. U. Kaikkonen, J. Seguin, Q. le Masne de Chermont, M. Bessodes, K. J. Airenne, S. Ylä-Herttuala, D. Scherman, and C. Richard, “In vitro targeting of avidin-expressing glioma cells with biotinylated persistent luminescence nanoparticles,” Bioconjug. Chem. 23(3), 472–478 (2012). [CrossRef] [PubMed]
15. L. Qin, Q. Zhu, G. Li, F. Liu, and Q. Pan, “Controlled fabrication of flower–like ZnO–Fe2O3 nanostructured films with excellent lithium storage properties through a partly sacrificed template method,” J. Mater. Chem. 22(15), 7544–7550 (2012). [CrossRef]
16. I. Tacchini, E. Terrado, A. Ansón, and M. Martinez, “Anatase nanotubes synthesized by a template method and their application as a green photocatalyst,” J. Mater. Sci. 46(7), 2097–2104 (2011). [CrossRef]
17. D. H. Wang, W. L. Zhou, B. F. McCaughy, J. E. Hampsey, X. L. Ji, Y. B. Jiang, H. F. Xu, J. K. Tang, R. H. Schmehl, C. O’Connor, C. J. Brinker, and Y. F. Lu, “Electrodeposition of metallic nanowire thin films using mesoporous silica templates,” Adv. Mater. 15(2), 130–133 (2003). [CrossRef]
18. H. Zhang, Z. Tan, P. Xu, K. Oh, R. Wu, W. Shi, and Z. Jiao, “Preparation of SnO2 nanowires by solvent-free method using mesoporous silica template and their gas sensitive properties,” J. Nanosci. Nanotechnol. 11(12), 11114–11118 (2011). [CrossRef] [PubMed]
19. J. Zong, Y. Zhu, X. Yang, J. Shen, and C. Li, “Synthesis of photoluminescent carbogenic dots using mesoporous silica spheres as nanoreactors,” Chem. Commun. 47(2), 764–766 (2011). [CrossRef] [PubMed]
20. Z. Li, H. Zhang, and H. Fu, “Facile synthesis and morphology control of Zn2SiO4:Mn nanophosphors using mesoporous silica nanoparticles as templates,” J. Lumin. 135, 79–83 (2013). [CrossRef]
21. L. Zhan-Jun, Z. Hong-Wu, S. Meng, S. Jiang-Shan, and F. Hai-Xia, “A facile and effective method to prepare long-persistent phosphorescent nanospheres and its potential application for in vivo imaging,” J. Mater. Chem. 22(47), 24713–24720 (2012). [CrossRef]
22. S. A. Hilderbrand and R. Weissleder, “Near-infrared fluorescence: application to in vivo molecular imaging,” Curr. Opin. Chem. Biol. 14(1), 71–79 (2010). [CrossRef] [PubMed]
23. Z. A. Qiao, L. Zhang, M. Y. Guo, Y. L. Liu, and Q. S. Huo, “Synthesis of mesoporous silica nanoparticles via controlled hydrolysis and condensation of silicon alkoxide,” Chem. Mater. 21(16), 3823–3829 (2009). [CrossRef]
24. A. Lecointre, A. Bessière, B. Viana, and D. Gourier, “Red persistent luminescent silicate nanoparticles,” Radiat. Meas. 45(3-6), 497–499 (2010). [CrossRef]
25. C. Wu, Y. Ramaswamy, and H. Zreiqat, “Porous diopside (CaMgSi2O6) scaffold: A promising bioactive material for bone tissue engineering,” Acta Biomater. 6(6), 2237–2245 (2010). [CrossRef] [PubMed]
