School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, 516 Jungong Road, Shanghai, 200093, China.
Dalton Trans. 2014 Apr 7;43(13):5142-50. doi: 10.1039/c3dt53433b.
We developed a potential immunostimulatory double-stranded DNA (dsDNA) delivery system by the binding of dsDNA to amino-modified mesoporous silica nanoparticles (MSNs) to form MSN-NH2/dsDNA complexes. Serum stability, in vitro cytotoxicity, cell uptake, and type I interferon-α (IFN-α) induction of MSN-NH2/dsDNA complexes were evaluated. The results showed that MSN-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and MSN-NH2/dsDNA complexes enhanced the serum stability of dsDNA due to the protection by nanoparticles and exhibited a high efficiency of cell uptake due to a small particle size and excellent dispersity. Most importantly, MSN-NH2/dsDNA complexes significantly enhanced the level of IFN-α induction, triggered by cytosolic DNA sensor proteins. Therefore, binding of immunostimulatory DNA to MSNs would play a promising role for enhancing the delivery efficiency of immunostimulatory DNA drugs.
我们通过将双链 DNA（dsDNA）与氨基修饰的介孔硅纳米粒子（MSNs）结合，形成 MSN-NH2/dsDNA 复合物，开发了一种潜在的免疫刺激双链 DNA （dsDNA）递药系统。评估了 MSN-NH2/dsDNA 复合物的血清稳定性、体外细胞毒性、细胞摄取和 I 型干扰素-α（IFN-α）诱导。结果表明，MSN-NH2 纳米粒子对 Raw 264.7 细胞没有细胞毒性，并且由于纳米粒子的保护，MSN-NH2/dsDNA 复合物增强了 dsDNA 的血清稳定性，并且由于粒径小和分散性好，具有高效的细胞摄取效率。最重要的是，MSN-NH2/dsDNA 复合物显著增强了细胞质 DNA 传感器蛋白触发的 IFN-α诱导水平。因此，免疫刺激 DNA 与 MSNs 的结合将为增强免疫刺激 DNA 药物的递药效率发挥有前途的作用。
