Silva Luisa H A, da Silva Jaqueline R, Ferreira Guilherme A, Silva Renata C, Lima Emilia C D, Azevedo Ricardo B, Oliveira Daniela M
IB-Departamento de Genética e Morfologia, Universidade de Brasília-UNB, Campus Universitário Darcy Ribeiro-Asa Norte, Brasília, DF, CEP 70910-970, Brazil.
Instituto de Química, Universidade Federal de Goias, Goiânia, GO, Brazil.
J Nanobiotechnology. 2016 Jul 18;14(1):59. doi: 10.1186/s12951-016-0213-x.
Nanoparticles' unique features have been highly explored in cellular therapies. However, nanoparticles can be cytotoxic. The cytotoxicity can be overcome by coating the nanoparticles with an appropriated surface modification. Nanoparticle coating influences biocompatibility between nanoparticles and cells and may affect some cell properties. Here, we evaluated the biocompatibility of gold and maghemite nanoparticles functionalized with 2,3-dimercaptosuccinic acid (DMSA), Au-DMSA and γ-Fe2O3-DMSA respectively, with human mesenchymal stem cells. Also, we tested these nanoparticles as tracers for mesenchymal stem cells in vivo tracking by computed tomography and as agents for mesenchymal stem cells magnetic targeting.
Significant cell death was not observed in MTT, Trypan Blue and light microscopy analyses. However, ultra-structural alterations as swollen and degenerated mitochondria, high amounts of myelin figures and structures similar to apoptotic bodies were detected in some mesenchymal stem cells. Au-DMSA and γ-Fe2O3-DMSA labeling did not affect mesenchymal stem cells adipogenesis and osteogenesis differentiation, proliferation rates or lymphocyte suppression capability. The uptake measurements indicated that both inorganic nanoparticles were well uptaken by mesenchymal stem cells. However, Au-DMSA could not be detected in microtomograph after being incorporated by mesenchymal stem cells. γ-Fe2O3-DMSA labeled cells were magnetically responsive in vitro and after infused in vivo in an experimental model of lung silicosis.
In terms of biocompatibility, the use of γ-Fe2O3-DMSA and Au-DMSA as tracers for mesenchymal stem cells was assured. However, Au-DMSA shown to be not suitable for visualization and tracking of these cells in vivo by standard computed microtomography. Otherwise, γ-Fe2O3-DMSA shows to be a promising agent for mesenchymal stem cells magnetic targeting.
纳米颗粒的独特特性在细胞治疗中得到了广泛研究。然而，纳米颗粒可能具有细胞毒性。通过用适当的表面修饰剂包覆纳米颗粒，可以克服这种细胞毒性。纳米颗粒的包覆会影响纳米颗粒与细胞之间的生物相容性，并可能影响某些细胞特性。在此，我们评估了分别用2,3 - 二巯基琥珀酸（DMSA）功能化的金纳米颗粒和磁赤铁矿纳米颗粒（Au - DMSA和γ - Fe2O3 - DMSA）与人间充质干细胞的生物相容性。此外，我们测试了这些纳米颗粒作为间充质干细胞体内追踪的示踪剂以及作为间充质干细胞磁靶向剂的性能。
在MTT、台盼蓝和光学显微镜分析中未观察到明显的细胞死亡。然而，在一些间充质干细胞中检测到超微结构改变，如线粒体肿胀和退化、大量髓鞘样结构以及类似于凋亡小体的结构。Au - DMSA和γ - Fe2O3 - DMSA标记不影响间充质干细胞的脂肪生成、成骨分化、增殖率或淋巴细胞抑制能力。摄取测量表明，两种无机纳米颗粒均能被间充质干细胞良好摄取。然而，Au - DMSA被间充质干细胞摄取后在显微断层扫描中无法检测到。γ - Fe2O3 - DMSA标记的细胞在体外以及在肺硅沉着病实验模型中体内注入后具有磁响应性。
就生物相容性而言，γ - Fe2O3 - DMSA和Au - DMSA作为间充质干细胞的示踪剂是可靠的。然而，Au - DMSA不适用于通过标准计算机显微断层扫描在体内可视化和追踪这些细胞。否则，γ - Fe2O3 - DMSA显示出是一种有前景的间充质干细胞磁靶向剂。
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