DNA can be used to nanofabricate three-dimensional (3D) polyhedra. A variety of applications of 3D DNA assemblies have been proposed. Drug encasulation and intracellular delivery using DNA nanoparticles, however, have remained a challenge. Here, we create a distinct five-point-star motif and aptamer-conjugated six-point-star motif using well-used primer sequences to intermolecularly construct DNA icosahedra as a nanocarrier for doxorubicin. Aptamer-conjugated doxorubicin-intercalated DNA icosahedra (Doxo@Apt-DNA-icosa) show an efficient and specific internalization for killing epithelial cancer cells.

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Tracking the distribution of stem cells is crucial to their therapeutic use. However, the usage of current vectors in cellular labeling is restricted by their low internalizing efficiency. Here, we reported a cellular labeling approach with a novel vector composed of mesoporous silica nanoparticles (MSNs) conjugated with fluorescein isothiocyanate in human bone marrow mesenchymal stem cells and 3T3-L1 cells, and the mechanism about fluorescein isothiocyanate-conjugated MSNs (FITC-MSNs) internalization was studied. FITC-MSNs were efficiently internalized into mesenchymal stem cells and 3T3-L1 cells even in short-term incubation. The process displayed a time- and concentration-dependent manner and was dependent on clathrin-mediated endocytosis. In addition, clathrin-dependent endocytosis seemed to play a decisive role on more internalization and longer stay of FITC-MSNs in mesenchymal stem cells than in 3T3-L1 cells. The internalization of FITC-MSNs did not affect the cell viability, proliferation, immunophenotype, and differentiation potential of mesenchymal stem cells, and 3T3-L1 cells. Finally, FITC-MSNs could escape from endolysosomal vesicles and were retained the architectonic integrity after internalization. We conclude that the advantages of biocompatibility, durability, and higher efficiency in internalization suit MSNs to be a better vector for stem cell tracking than others currently used.

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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][6][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 con-trast agent [10][11][12][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][18][19] Previously, we reported multimodal tumblerlike mesoporous silica, which carries a magnetic iron oxide nanoparticle as a T 2 contrast agent (T 1 and T 2 = magnetic relaxation times) and a fluorescent dye. [20] However, the T 2 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 T 1 and T 2 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 T 2 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 o...

The progress of using gadolinium (Gd)-based nanoparticles in cellular tracking lags behind that of superparamagnetic iron oxide (SPIO) nanoparticles in magnetic resonance imaging (MRI). Here, dual functional Gd-fluorescein isothiocyanate mesoporous silica nanoparticles (Gd-Dye@MSN) that possess green fluorescence and paramagnetism are developed in order to evaluate their potential as effective T1-enhancing trackers for human mesenchymal stem cells (hMSCs). hMSCs are labeled efficiently with Gd-Dye@MSN via endocytosis. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes, osteocytes, and chondrocytes, which can still be readily MRI detected. Imaging, with a clinical 1.5-T MRI system and a low incubation dosage of Gd, low detection cell numbers, and short incubation times is demonstrated on both loaded cells and hMSC-injected mouse brains. This study shows that the advantages of biocompatibility, durability, high internalizing efficiency, and pore architecture make MSNs an ideal vector of T1-agent for stem-cell tracking with MRI.

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