High-contrast paramagnetic fluorescent mesoporous silica nanorods as a multifunctional cell-imaging probe
High-contrast paramagnetic fluorescent mesoporous silica nanorods as a multifunctional cell-imaging probe
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DOI：
10.1002/smll.200700457
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发表时间：
2008-02-01
期刊：
影响因子：
13.3
通讯作者：
Mou, Chung-Yuan
中科院分区：
文献类型：
--
作者：
Tsai, Chih-Pin;Hung, Yann;Mou, Chung-Yuan
细胞作为治疗剂有许多优点。它们能够执行复杂的功能，如在干细胞或免疫细胞治疗中为了获得有效的治疗，被输送的细胞必须携带长寿命的追踪剂，以监测被注射细胞的位置和命运。目前，监测通常通过缓慢的组织学分析进行，这需要组织活检。近年来，注射细胞的无创实时跟踪技术的发展因其临床潜力而备受关注。荧光纳米材料已经成功地用作生物和医学成像[3,4]和诊断用途的标签。[5-7]荧光技术检测深层组织的能力有限，限制了体内信息的收集。磁共振成像（MRI）是一种重要的无创成像技术，已广泛应用于临床诊断和生物医学研究。然而，对于细胞水平的应用，它的灵敏度相对较低因此，合成一种新型的高灵敏度MRI造影剂[10-13]将会引起人们极大的兴趣。近年来，基于纳米材料的多功能探针的开发已成为一个非常活跃的领域。最好的是，这些功能应该结合MRI的无创性、荧光的高灵敏度和分辨率、靶向的表面官能团和局部递送药物的能力。其中，携带良好且寿命长的MRI造影剂将是最有用的。我们的兴趣是开发一种纳米形式的介孔二氧化硅，它具有一些独特的性质，如刚性结构，大孔体积，均匀的孔径，良好的表面修饰能力，[14]和良好的生物相容性。它也被证明是一种生物标志物[15,16]和药物载体。[17-19]之前，我们报道了多模态杯状介孔二氧化硅，它携带磁性氧化铁纳米颗粒作为T2造影剂（T1和T2=磁弛豫时间）和荧光染料然而，T2显影剂在深色区域（如肝脏）的造影剂造影效果较差。本文报道了一种新的多功能介孔二氧化硅纳米棒，具有绿色荧光和顺磁性，可以作为T1和T2成像的良好造影剂。基于纳米颗粒的多模态监测剂在此之前已经发展起来。然而，很少被证明是细胞监测的平台有几种不同的发光材料、MRI造影剂和支架的组合。氧化铁纳米颗粒，一种典型的T2造影剂，已被证明是一个多模态探针与Cy5的表面功能化。5染料和氯毒素检测胶质瘤Santra及其同事还通过将Gd-TSPETE （n-三甲氧基硅丙基）乙基二胺三乙酸三钠盐)和CdSe: Mn/ZnS核壳量子点或Gd-TSPETE和[RuACHTUNGTRENNUNG (bpy) 3] 2+（bpy= 2,2 ' -联吡啶）包封在二氧化硅基体中，开发了新型多功能探针。[23,24]这两种杂化二氧化硅纳米颗粒的横向弛豫速率（1/T2）均大于纵向弛豫速率（1/T1），作为T2造影剂的作用更好。因此，开发一种具有t1加权成像增强的多功能药物是可取的，最近有一些报道；例如，包裹有顺磁性聚乙二醇脂质[25]（PEG=聚乙二醇）和gd -DTTA修饰（DTTA：二乙烯三胺四乙酸酯）掺杂[RuACHTUNGTRENNUNG (bpy) 3] 2+.[26]的硅球的量子点多功能纳米棒是…
Cells have many advantages as therapeutic agents. They are able to carry out complex functions, as in stem cell [1] or immune cell therapy.[2] For effective therapy, the delivered cells must carry long-lived tracking agents for monitoring the position and fate of the injected cells. At present, monitoring is often carried out by slow histological analysis, which requires tissue biopsy. Recently, the development of noninvasive real-time tracking of injected cells has attracted a lot of attention for its clinical potential. Fluorescent nanomaterials have been successfully utilized as labels in biological and medical applications for imaging [3, 4] and diagnostic purposes.[5–7] The limited capability of the fluorescence technique in detecting deep tissues restricts the collection of information in vivo. Magnetic resonance imaging (MRI), one of the most important noninvasive imaging techniques, has been widely used for clinical diagnosis [8] and biomedical research. However, its sensitivity is relatively low for cellularlevel applications.[9] Hence, the synthesis of a new MRI contrast agent [10–13] with high sensitivity would be of great interest.Recently, the development of a nanomaterial-based probe with multifunctionalities has become a very active field. Preferably, the functionalities should combine the advantages of MRI in noninvasiveness, fluorescence in high sensitivity and resolution, a surface functional group for targeting, and the ability to deliver drugs locally. Among these, the carrying of good and long-lived MRI contrast agents would be the most useful. Our interest is in developing a nanoparticle form of mesoporous silica, which has some unique properties, such as rigid structure, large pore volume, uniform pore size, great surface-modification capability,[14] and good biocompatibility. It has also been demonstrated as a biomarker [15, 16] and a drug carrier.[17–19] Previously, we reported multimodal tumblerlike mesoporous silica, which carries a magnetic iron oxide nanoparticle as a T2 contrast agent (T1 and T2= magnetic relaxation times) and a fluorescent dye.[20] However, the T2 agent often gives poor contrast in dark areas, such as the liver. Herein, we report a new multifunctional mesoporous silica nanorod that possesses green fluorescence and paramagnetism, and could serve as a good contrast agent in T1 and T2 imaging. The multimodality of nanoparticle-based monitoring agents has been developed before. However, very few have been demonstrated as a platform in cell monitoring.[21] There are several different combinations of luminescent materials, MRI contrast agents, and support. The iron oxide nanoparticle, a typical T2 contrast agent, has been demonstrated to be a multimodal probe by surface functionalization with Cy5. 5 dye and chlorotoxin to detect gliomas.[22] Santra and co-workers also developed novel multifunctional probes by encapsulating Gd-TSPETE (n-trimethoxysilylpropyl) ethyldiamine triacetic acid trisodium salt) and CdSe: Mn/ZnS core–shell quantum dots or Gd-TSPETE and [RuACHTUNGTRENNUNG (bpy) 3] 2+(bpy= 2, 2’-bipyridine) in a silica matrix.[23, 24] Both hybrid silica nanoparticles increase the transverse relaxation rate (1/T2) more than the longitudinal relaxation rate (1/T1), and function better as T2 contrast agents. The development of a multifunctional agent with T1-weighted imaging enhancement is thus desirable and some have been reported recently; for example, quantum dots coated with paramagnetic PEGylated lipid [25](PEG= polyethylene glycol) and Gd-DTTA-modified (DTTA: diethylenetriaminetetraacetate) silica spheres doped with [RuACHTUNGTRENNUNG (bpy) 3] 2+.[26] The multifunctional nanorods were …