Cellular Internalization-Induced Aggregation of Porous Silicon Nanoparticles for Ultrasound Imaging and Protein-Mediated Protection of Stem Cells
Cellular Internalization-Induced Aggregation of Porous Silicon Nanoparticles for Ultrasound Imaging and Protein-Mediated Protection of Stem Cells
复制标题
细胞内化——诱导多孔硅纳米粒子聚集，用于超声成像和蛋白质——介导的干细胞保护
DOI：
10.1002/smll.201804332
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发表时间：
2019-01-04
期刊：
影响因子：
13.3
通讯作者：
Zhang, Hongbo
中科院分区：
文献类型：
--
作者：
Qi, Shengcai;Zhang, Pengfei;Zhang, Hongbo
纳米技术采用纳米级范围内的多功能工程材料，为转化干细胞研究和治疗提供了许多机会。在这里，提出了一种细胞穿透肽（病毒-1转录反式激活因子）缀合的多孔硅纳米颗粒（TPSi NP），其装载有Wnt 3a蛋白，以通过组合治疗诊断策略增加细胞存活率和干细胞移植的递送精度。具有10.7 nm孔径和无机骨架的TPSi NP能够高效负载Wnt 3a，抑制Wnt 3a释放，并增加标记的间充质干细胞（MSC）中的抗氧化应激活性，这对于心肌梗死干细胞治疗中的细胞保护是非常有益的特性。证实了TPSi NPs的细胞内聚集可以高度放大标记的MSC的声散射，导致与未标记的MSC相比超声（US）信号增加2.3倍。通过在裸鼠模型中心肌内注射标记的MSC，证实了所设计的用于实时US成像引导的干细胞移植的纳米剂的翻译潜力。有人提出，负载蛋白质药物的TPSi纳米颗粒的细胞内聚集可能是提高干细胞治疗效果的一种简单但稳健的策略。
Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.