CN101670107B - Multifunctional core-shell structure drug carrier material and preparation method thereof - Google Patents
Multifunctional core-shell structure drug carrier material and preparation method thereof Download PDFInfo
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Abstract
Description
(一)技术领域(1) Technical field
本发明涉及的是一种核壳结构药物载体材料。本发明还涉及一种核壳结构药物载体材料的制备方法。The invention relates to a drug carrier material with a core-shell structure. The invention also relates to a preparation method of a drug carrier material with a core-shell structure.
(二)背景技术(2) Background technology
核壳结构材料可以很好的发挥壳材料与核材料各自的最大优势。核材料在包覆额外的壳层后，依旧保留其固有的特性，同时其表面电荷密度、功能性、反应性、生物相容性、稳定性及分散性等表面特性受到壳材料的调整和优化，可能因此产生许多新的特性，因此核壳型纳米颗粒在触媒、光学、电磁学、生物、医学及高性能机械材料等诸方面皆具有极大的发展潜力与应用价值。结合磁性、荧光的壳核结构有序介孔材料由于其磁性、荧光、低毒性、良好的生物相容性以及介孔等性质在疾病分析、酶的固化、生物分离及药物缓释领域得到广泛研究。The core-shell structure materials can give full play to the respective maximum advantages of the shell material and the core material. After the core material is coated with an additional shell layer, it still retains its inherent characteristics, and its surface characteristics such as surface charge density, functionality, reactivity, biocompatibility, stability, and dispersion are adjusted and optimized by the shell material Therefore, core-shell nanoparticles have great development potential and application value in various aspects such as catalysts, optics, electromagnetics, biology, medicine and high-performance mechanical materials. The ordered mesoporous materials with a shell-core structure combined with magnetism and fluorescence have been widely used in the fields of disease analysis, enzyme immobilization, bioseparation and drug sustained release due to their magnetic properties, fluorescence, low toxicity, good biocompatibility and mesoporous properties. Research.
迄今为止，一些文献报道了磁性物质为核、二氧化硅为壳的壳核结构的多功能复合材料。一些荧光材料如有机染料、CdSe/ZnS量子点随后功能化于表面或形成壳的一部分，最终制成具备磁性、荧光及有序介孔多功能性质的壳核结构材料。但有机染料作为荧光物质具有荧光衰减和淬灭的缺点，而量子点由于使用Cd2+及Pb2+等重金属而严重限制了其在生物医学领域的应用，尤其是人体实验的应用。最近，随着上转换荧光材料的研究初见成效，已经有将其应用于磁性及荧光材料的报道。然而，在生物领域具备高活性的功能化材料要求具备一些独特的性质，如规整球形形貌、光滑的表面、小的粒径分布、大的比表面(用于药物分子、酶和蛋白质的担载和固化)、大的磁强度(用以提供足够的磁场信号)以及在溶液中具有良好的分散性质等等。因此，设计制备这样一种具有上述性质的独特的多功能化材料在生物医学领域具有良好的应用前景。So far, some literatures have reported multifunctional composite materials with a core-shell structure in which the magnetic substance is the core and the silica is the shell. Some fluorescent materials such as organic dyes and CdSe/ZnS quantum dots are then functionalized on the surface or form part of the shell, and finally a core-shell structure material with magnetic, fluorescent and ordered mesoporous multifunctional properties is produced. However, as fluorescent substances, organic dyes have the disadvantages of fluorescence attenuation and quenching, and the use of heavy metals such as Cd 2+ and Pb 2+ in quantum dots severely limits their applications in the field of biomedicine, especially in human experiments. Recently, as the research on up-conversion fluorescent materials has achieved initial results, there have been reports on its application to magnetic and fluorescent materials. However, functionalized materials with high activity in the biological field require some unique properties, such as regular spherical morphology, smooth surface, small particle size distribution, and large specific surface area (for loading of drug molecules, enzymes and proteins). Loading and solidification), large magnetic strength (to provide sufficient magnetic field signal), and good dispersion properties in solution, etc. Therefore, designing and preparing such a unique multifunctional material with the above properties has a good application prospect in the field of biomedicine.
镧系稀土离子掺杂的无机纳米晶体由于其稳定的光学性质、高的化学及光化学稳定性以及低毒性等特点已经成为有机染料和量子点的替代品。尤其是之前提到的纳米尺度的上转换荧光材料，它作为一种新型荧光标记物在生物大分子检测方面的应用近几年来逐渐受到研究人员的重视，相关报道日益增多。与传统荧光标记物如有机染料和量子点等相比，上转换荧光纳米材料具有毒性低、化学稳定性好、发光强度高而稳定和
(三)发明内容(3) Contents of the invention
本发明的目的在于提供一种纯度高、粒径小、分散性好、晶形好的多功能核壳结构药物载体材料；本发明的目的还在于提供一种在减小材料粒径大小和提高材料分散性的同时，能提高其磁性、荧光可检测性和吸附等应用能力的多功能核壳结构药物载体材料的制备方法。The purpose of the present invention is to provide a drug carrier material with a multifunctional core-shell structure with high purity, small particle size, good dispersibility and good crystal form; A preparation method for a multifunctional core-shell drug carrier material that can improve its magnetic properties, fluorescence detectability, and adsorption and other application capabilities while dispersing.
本发明的目的是这样实现的：The purpose of the present invention is achieved like this:
本发明的多功能核壳结构药物载体材料的化学表达式为：The chemical expression of the multifunctional core-shell structure drug carrier material of the present invention is:
Fe3O4@nSiO2@mSiO2@NaYF4:Yb，ErFe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 : Yb, Er
其中nSiO2代表无孔二氧化硅层；mSiO2代表介孔二氧化硅层；NaYF4:Yb，Er为最外层负载的上转换荧光粉层，其中Yb的摩尔浓度占Y浓度的17％，Er的摩尔浓度占Y浓度的3％。Wherein nSiO 2 represents a non-porous silicon dioxide layer; mSiO 2 represents a mesoporous silicon dioxide layer; NaYF 4 : Yb, Er is the up-conversion phosphor layer loaded on the outermost layer, wherein the molar concentration of Yb accounts for 17% of the Y concentration , the molar concentration of Er accounts for 3% of the Y concentration.
本发明的多功能核壳结构药物载体材料的制备方法为：第一步采用溶剂热法制备粒60nm、单分散的四氧化三铁磁性纳米粒子作为核壳结构的强磁性核材料；第二步采用溶胶-凝胶法在强磁性核外依次包覆一层无孔二氧化硅层和一层介孔二氧化硅层；第三步再次采用溶胶-凝胶法在第二步得到的材料上负载一层上转换荧光材料NaYF4:Yb，Er，其中Yb的摩尔浓度占Y浓度的17％，Er的摩尔浓度占Y浓度的3％。The preparation method of the multifunctional core-shell structure drug carrier material of the present invention is as follows: the first step adopts the solvothermal method to prepare 60nm, monodisperse ferroferric oxide magnetic nanoparticles as the strong magnetic core material of the core-shell structure; the second step Using the sol-gel method to coat a layer of non-porous silica layer and a layer of mesoporous silica layer on the outside of the strong magnetic core in turn; the third step is to use the sol-gel method again on the material obtained in the second step A layer of up-conversion fluorescent material NaYF 4 :Yb, Er is loaded, wherein the molar concentration of Yb accounts for 17% of the Y concentration, and the molar concentration of Er accounts for 3% of the Y concentration.
(1)所述采用溶剂热法制备强磁性核材料是：将1g FeCl3·6H2O、20mL乙二醇、3g无水乙酸钠和10mL乙二胺均匀混合后在200℃反应釜中反应12小时，80℃干燥并研磨制备Fe3O4纳米粒子。(1) The preparation of the ferromagnetic core material by the solvothermal method is as follows: 1g FeCl 3 6H 2 O, 20mL ethylene glycol, 3g anhydrous sodium acetate and 10mL ethylenediamine are evenly mixed and then reacted in a 200°C reactor For 12 hours, dry at 80°C and grind to prepare Fe 3 O 4 nanoparticles.
(2)所述采用溶胶-凝胶法在强磁性核外依次包覆一层无孔二氧化硅层和一层介孔二氧化硅层是：采用修饰的
(3)所述采用溶胶-凝胶法在第二步得到的材料上负载一层上转换荧光材料NaYF4:Yb，Er是：采用Pechini溶胶-凝胶过程将NaYF4:Yb，Er发光粉沉积在介孔二氧化硅上；发光粉中Yb的摩尔浓度占Y浓度的17％，Er的摩尔浓度占Y浓度的3％；将NaF和Fe3O4@nSiO2@mSiO2微球按质量比为21∶1超声分散到去离子水中，得到分散均匀的混合物；再按化学计量比分别量取浓度为0.2mol/L的YCl3、YbCl3、ErCl3和EDTA溶液配置成混合溶液；将配好的混合溶液迅速添加到已超声分散均匀的混合物中，得到的最终混合物在室温下搅拌反应4h；最后用强磁场将反应后的产物分离出来，并用去离子水洗涤并干燥；得到的是未焙烧的多功能材料微球Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er；未焙烧的多功能材料微球Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er放入箱式电阻炉中焙烧，就得到了多功能的核壳结构纳米微球Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er。(3) the adoption of the sol-gel method to load one layer of up-conversion fluorescent material NaYF 4 : Yb on the material obtained in the second step, Er is: adopting the Pechini sol-gel process to use NaYF 4 : Yb, Er luminescent powder Deposited on mesoporous silica; the molar concentration of Yb in the luminescent powder accounts for 17% of the Y concentration, and the molar concentration of Er accounts for 3% of the Y concentration; the NaF and Fe 3 O 4 @nSiO 2 @mSiO 2 microspheres are pressed Ultrasonic dispersion in deionized water with a mass ratio of 21:1 to obtain a uniformly dispersed mixture; then measure YCl 3 , YbCl 3 , ErCl 3 and EDTA solutions with a concentration of 0.2 mol/L according to the stoichiometric ratio to prepare a mixed solution; The prepared mixed solution was quickly added to the ultrasonically dispersed mixture, and the resulting final mixture was stirred and reacted at room temperature for 4 hours; finally, the reacted product was separated with a strong magnetic field, washed with deionized water and dried; the obtained Uncalcined multifunctional material microspheres Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er; uncalcined multifunctional material microspheres Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb , Er was put into a box-type resistance furnace and roasted, and the multifunctional core-shell nanospheres Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er were obtained.
本发明针对背景技术中所述的磁性、荧光及介孔核壳结构材料存在的缺陷，提出了：①在磁性核和后功能化的稀土发光材料之间设计一层惰性SiO2层将磁性材料与稀土发光层分开以防止荧光淬灭；②采用荧光效率较高的上转换荧光粉作为发光材料；③采用反应条件温和、分散均匀的溶胶-凝胶法形成核壳结构。尽管国内外学者对功能化的核壳结构材料的配方和应用研究做了大量工作，但是，具有强磁性、上转换荧光性及介孔性的药物缓/控释载体材料的制备及相关理论尚属空白。The present invention aims at the defects of the magnetic, fluorescent and mesoporous core-shell structure materials described in the background technology, and proposes: 1. design a layer of inert SiO2 layer between the magnetic core and the post-functionalized rare earth luminescent material to make the magnetic material Separate from the rare earth light-emitting layer to prevent fluorescence quenching; ②Use up-conversion phosphor with high fluorescence efficiency as the luminescent material; ③Use the sol-gel method with mild reaction conditions and uniform dispersion to form a core-shell structure. Although scholars at home and abroad have done a lot of work on the formulation and application of functionalized core-shell materials, the preparation and related theories of drug slow/controlled release carrier materials with strong magnetism, up-conversion fluorescence and mesopority are still unknown. is blank.
在磁性核外先包覆的无孔二氧化硅惰性层可以将磁性材料与稀土发光层分开以防止荧光淬灭。此外，负载的红外到可见波段的上转换荧光材料NaYF4:Yb，Er赋予了材料更强的荧光性、稳定性、不褪色和不易受环境(如缓冲剂pH值或分析温度)影响等性能。The non-porous silicon dioxide inert layer coated outside the magnetic core can separate the magnetic material from the rare earth light-emitting layer to prevent fluorescence quenching. In addition, the loaded up-conversion fluorescent material NaYF 4 : Yb in the infrared to visible band, Er endows the material with stronger fluorescence, stability, non-fading and less susceptible to the environment (such as buffer pH value or analysis temperature) and other properties .
本发明采用溶剂热法制备Fe3O4纳米粒子。此法具有两个特点，一是较高的反应温度(130～250℃)，有利于磁性能的提高；二是在封闭容器中进行，产生相对高压(0.3～4MPa)，避免组分挥发，有利于提高产物的纯度。同时还具有原料易得、粒子纯度高、粒径小、分散性好、晶形好等优点。本发明采用两步溶胶-凝胶法对磁性纳米粒子进行介孔及NaYF4:Yb，Er荧光层包覆，该法较其它方法具有反应条件温和、分散均匀、甚至可达到“分子复合”的水平、可在低温下制备纯度高、粒径分布均匀、化学活性大的单组分或多组分分子级混合物，以及可制备传统方法不能或难以制得的产物等优点。The invention adopts a solvothermal method to prepare Fe3O4nanoparticles . This method has two characteristics, one is a higher reaction temperature (130-250°C), which is beneficial to the improvement of magnetic properties; the other is that it is carried out in a closed container to generate relatively high pressure (0.3-4MPa) to avoid volatilization of components. It is beneficial to improve the purity of the product. At the same time, it also has the advantages of easy access to raw materials, high particle purity, small particle size, good dispersibility, and good crystal form. The present invention uses a two-step sol-gel method to coat the magnetic nanoparticles with mesoporous and NaYF 4 :Yb, Er fluorescent layers. Compared with other methods, this method has the advantages of mild reaction conditions, uniform dispersion, and even "molecular compounding" High purity, uniform particle size distribution, high chemical activity single-component or multi-component molecular-level mixtures can be prepared at low temperature, and products that cannot or are difficult to obtain by traditional methods can be prepared.
(四)附图说明(4) Description of drawings
图1中(a)、(b)、(c)、(d)分别为Fe3O4纳米粒子、Fe3O4@nSiO2@mSiO2微球、Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er(未焙烧)和Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的XRD谱图。(a), (b), (c) and (d) in Figure 1 are Fe 3 O 4 nanoparticles, Fe 3 O 4 @nSiO 2 @mSiO 2 microspheres, Fe 3 O 4 @nSiO 2 @mSiO 2 XRD patterns of @NaYF 4 :Yb, Er (uncalcined) and Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er microspheres.
图2(a)和图2(b)是Fe3O4纳米粒子的SEM图；图2(c)和图2(d)是Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的SEM图。Figure 2(a) and Figure 2(b) are SEM images of Fe 3 O 4 nanoparticles; Figure 2(c) and Figure 2(d) are Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, SEM images of Er microspheres.
图3(a)和图3(c)分别是Fe3O4纳米粒子的TEM和HRTEM图；图3(b)和图3(d、e)分别是Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的TEM和HRTEM图。Figure 3(a) and Figure 3(c) are TEM and HRTEM images of Fe 3 O 4 nanoparticles, respectively; Figure 3(b) and Figure 3(d, e) are Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 : TEM and HRTEM images of Yb, Er microspheres.
图4(a)是Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的XPS总谱图；图4(b)、图4(c)、图4(d)、图4(e)和图4(f)是图4(a)的局部放大图。Figure 4(a) is the XPS spectrum of Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er microspheres; Figure 4(b), Figure 4(c), Figure 4(d), and 4(e) and FIG. 4(f) are partial enlarged views of FIG. 4(a).
图5分别是Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的发射光谱。Figure 5 is the emission spectra of Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb and Er microspheres, respectively.
图6(a)、图6(b)和图6(c)分别为Fe3O4纳米粒子、Fe3O4@nSiO2@mSiO2微球和Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的磁滞回线图；图6(d)是Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的磁分离过程示图。Figure 6(a), Figure 6(b) and Figure 6(c) are Fe 3 O 4 nanoparticles, Fe 3 O 4 @nSiO 2 @mSiO 2 microspheres and Fe 3 O 4 @nSiO 2 @mSiO 2 @ Hysteresis loop diagram of NaYF 4 :Yb, Er microspheres; Figure 6(d) is a diagram of the magnetic separation process of Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er microspheres.
(五)具体实施方式(5) Specific implementation methods
下面举例对本发明做更详细地描述：The following examples describe the present invention in more detail:
实施过程1：Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的合成Implementation process 1: Synthesis of Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er microspheres
①Fe3O4纳米粒子的制备① Preparation of Fe 3 O 4 nanoparticles
采用溶剂热法，先将1g FeCl3·6H2O、20mL乙二醇、3g无水乙酸钠和10mL乙二胺混合并强烈搅拌30min，形成透明溶液。然后将所得溶液转移到封闭的聚四氟乙烯作内衬的不锈钢反应釜中，在200℃下反应12h。反应后自然冷却到室温。将反应产物用水和无水乙醇洗涤数次，最后在80℃干燥12h并研磨成粉末就得到了Fe3O4纳米粒子。Using solvothermal method, first mix 1g FeCl 3 ·6H 2 O, 20mL ethylene glycol, 3g anhydrous sodium acetate and 10mL ethylenediamine and stir vigorously for 30min to form a transparent solution. Then the obtained solution was transferred to a closed polytetrafluoroethylene-lined stainless steel reactor, and reacted at 200° C. for 12 h. After the reaction, it was naturally cooled to room temperature. The reaction product was washed several times with water and absolute ethanol, and finally dried at 80° C. for 12 h and ground into powder to obtain Fe 3 O 4 nanoparticles.
②Fe3O4@nSiO2磁性微球的制备②Preparation of Fe 3 O 4 @nSiO 2 magnetic microspheres
壳核结构的Fe3O4@nSiO2微球采用修饰的
③Fe3O4@nSiO2@mSiO2磁性及介孔核壳结构纳米微球的制备③Preparation of Fe 3 O 4 @nSiO 2 @mSiO 2 magnetic and mesoporous core-shell nanospheres
将步骤②制备的Fe3O4@nSiO2粒子分散到溶解有0.3g十六烷基三甲基溴化铵(CTAB)、80mL去离子水、1.0mL浓氨水和60mL无水乙醇的混合溶液中。此混合溶液搅拌30min后，在激烈搅拌下加入0.40g正硅酸乙脂(TEOS)。体系反应6h，得到的产物经强磁场进行分离，用无水乙醇和去离子水洗涤数次再用离心机分离。最后80℃干燥12h，研磨，得到的产物即为在Fe3O4@nSiO2磁性微球表面包覆了介孔SiO2的磁性及介孔核壳结构纳米微球。上述包覆过程重复两次。由于形成介孔使用了模板剂CTAB，而介孔中的模板剂CTAB尚未除去，是以我们将此产物表示为Fe3O4@nSiO2@mSiO2-CTAB。Disperse the Fe 3 O 4 @nSiO 2 particles prepared in
采用回流法除掉上述产物(Fe3O4@nSiO2@mSiO2-CTAB)介孔孔道中残留的模板剂CTAB。具体过程如下：(1)将0.6g Fe3O4@nSiO2@mSiO2-CTAB样品和120mL丙酮加入到三口烧瓶中，将三口烧瓶置于75℃油域(二甲基硅油)中回流48h；(2)将回流后的样品用强磁场分离后用丙酮洗涤一次，再加入120mL丙酮回流48h；(3)重复步骤(2)一次，将得到的样品用丙酮洗涤两次，放到低温干燥箱中干燥，再经过研磨就得到了除去模板剂的磁性及介孔核壳结构纳米微球，表示为Fe3O4@nSiO2@mSiO2。The template agent CTAB remaining in the mesoporous channels of the above product (Fe 3 O 4 @nSiO 2 @mSiO 2 -CTAB) was removed by reflux. The specific process is as follows: (1) Add 0.6g Fe 3 O 4 @nSiO 2 @mSiO 2 -CTAB sample and 120mL acetone into a three-necked flask, and place the three-necked flask in a 75°C oil domain (simethicone) to reflux for 48h (2) wash the sample with acetone once after being separated by a strong magnetic field, then add 120mL of acetone to reflux for 48h; (3) repeat step (2) once, wash the obtained sample twice with acetone, and dry it at low temperature The magnetic and mesoporous core-shell nanospheres without the template were obtained after drying in the oven, and then grinding, expressed as Fe 3 O 4 @nSiO 2 @mSiO 2 .
④Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er微球的制备④Preparation of Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er microspheres
采用溶胶-凝胶法制备，具体实验步骤如下：将2.1g NaF和0.100gFe3O4@nSiO2@mSiO2微球超声(45min)分散到120mL去离子水中，得到分散均匀的混合物。再分别量取浓度为0.2mol/L的YCl3、YbCl3、ErCl3和EDTA各16mL、3.4mL、0.6mL和20mL配置成混合溶液。将配好的混合溶液迅速添加到已超声45min的混合物中，得到的最终混合物在室温下搅拌反应4h。最后用强磁场将反应后的产物分离出来，并用去离子水洗涤一次，放到低温干燥箱中干燥12h。得到的是未焙烧的多功能材料微球，表示为Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er(未焙烧)，上述包覆过程重复两次。It was prepared by sol-gel method, and the specific experimental steps were as follows: 2.1g NaF and 0.100gFe 3 O 4 @nSiO 2 @mSiO 2 microspheres were ultrasonically dispersed (45min) into 120mL deionized water to obtain a uniformly dispersed mixture. Then measure 16mL, 3.4mL, 0.6mL and 20mL of each of YCl 3 , YbCl 3 , ErCl 3 and EDTA with a concentration of 0.2 mol/L to prepare a mixed solution. The prepared mixed solution was quickly added to the mixture that had been sonicated for 45 min, and the resulting final mixture was stirred and reacted at room temperature for 4 h. Finally, the reacted product was separated by a strong magnetic field, washed once with deionized water, and dried in a low-temperature drying oven for 12 hours. The obtained unbaked multifunctional material microspheres are expressed as Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er (unbaked), and the above coating process is repeated twice.
上述样品放入箱式电阻炉中焙烧。焙烧从室温开始，以20℃/min的速度程序升温到400℃，并在400℃焙烧5h，再自然冷却到室温，研磨成粉末样品，就得到了多功能(磁性、介孔和荧光)的核壳结构纳米微球，表示如下：Fe3O4@nSiO2@mSiO2@NaYF4:Yb，Er。The above samples were fired in a box-type resistance furnace. The calcination starts from room temperature, the temperature is programmed to rise to 400 ℃ at a rate of 20 ℃/min, and it is baked at 400 ℃ for 5 hours, then naturally cooled to room temperature, and ground into a powder sample to obtain a multifunctional (magnetic, mesoporous and fluorescent) The core-shell nanospheres are expressed as follows: Fe 3 O 4 @nSiO 2 @mSiO 2 @NaYF 4 :Yb, Er.
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