Cheng Jin, Ding Qian, Wang Jia, Deng Lin, Yang Lu, Tao Lei, Lei Haihong, Lu Shaoping
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Department of Anesthesiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Nanoscale. 2016 Jan 28;8(4):2011-21. doi: 10.1039/c5nr08560h.
Heart disease is one of the deadliest diseases causing mortality due to the limited regenerative capability of highly differentiated cardiomyocytes. Stem cell-based therapy in tissue engineering is one of the most exciting and rapidly growing areas and raises promising prospects for cardiac repair. In this study, we have synthesized FITC-mesoporous silica nanoparticles (FMSNs) based on a sol-gel method (known as Stöber's method) as a drug delivery platform to transport 5-azacytidine in P19 embryonic carcinoma stem cells. The surfactant CTAB is utilized as a liquid crystal template to self-aggregate into micelles, resulting in the synthesis of MSNs. Based on the cell viability assay, treatment with FMSNs + 5-azacytidine resulted in much more significant inhibition of the proliferation than 5-azacytidine alone. To study the mechanism, we have tested the differentiation genes and cardiac marker genes in P19 cells and found that these genes have been up-regulated in P19 embryonic carcinoma stem cells treated with FMSNs + 5-azacytidine + poly(allylamine hydrochloride) (PAH), with the changes of histone modifications on the regulatory region. In conclusion, with FMSNs as drug delivery platforms, 5-azacytidine can be more efficiently delivered into stem cells and can be used to monitor and track the transfection process in situ to clarify their effects on stem cell functions and the differentiation process, which can serve as a promising tool in tissue engineering and other biomedical fields.
由于高度分化的心肌细胞再生能力有限，心脏病是导致死亡的最致命疾病之一。组织工程中基于干细胞的疗法是最令人兴奋且发展迅速的领域之一，为心脏修复带来了充满希望的前景。在本研究中，我们基于溶胶 - 凝胶法（即施托伯法）合成了异硫氰酸荧光素 - 介孔二氧化硅纳米颗粒（FMSNs），作为一种药物递送平台，用于在P19胚胎癌细胞中运输5 - 氮杂胞苷。表面活性剂十六烷基三甲基溴化铵（CTAB）被用作液晶模板自聚集形成胶束，从而合成介孔二氧化硅纳米颗粒（MSNs）。基于细胞活力测定，FMSNs + 5 - 氮杂胞苷处理比单独使用5 - 氮杂胞苷对细胞增殖的抑制作用更显著。为了研究其机制，我们检测了P19细胞中的分化基因和心脏标记基因，发现这些基因在用FMSNs + 5 - 氮杂胞苷 + 聚（烯丙胺盐酸盐）（PAH）处理的P19胚胎癌细胞中上调，同时调控区域的组蛋白修饰也发生了变化。总之，以FMSNs作为药物递送平台，5 - 氮杂胞苷能够更有效地递送至干细胞中，并可用于原位监测和追踪转染过程，以阐明其对干细胞功能和分化过程的影响，这可成为组织工程及其他生物医学领域中一种有前景的工具。
