Bone Formation Promoted by Bone Morphogenetic Protein-2 Plasmid-Loaded Porous Silica Nanoparticles with the Involvement of Autophagy
Bone Formation Promoted by Bone Morphogenetic Protein-2 Plasmid-Loaded Porous Silica Nanoparticles with the Involvement of Autophagy
复制标题
骨形态发生蛋白-2质粒负载的多孔二氧化硅纳米颗粒通过自噬促进骨形成
DOI：
10.1039/c9nr07017f
复制
发表时间：
2019
期刊：
影响因子：
6.7
通讯作者：
Sun Hongchen
中科院分区：
文献类型：
--
作者：
Xu Xiao Wei;Sun Mao Lei;Wang Dan Dan;Bu Wen Huan;Wang Zi Lin;Shen Yu Qin;Zhang Kai;Zhou Ding;Yang Bai;Sun Hongchen
基因治疗是修复缺损骨组织最常用和最有效的方法之一，但即使是高效的基因传递载体也是不够的。本研究采用乙醚乳液法合成了聚乙烯亚胺修饰的多孔二氧化硅纳米颗粒(PPSNs)，并将其包裹在骨形态发生蛋白-2(BMP-2)载体上。由于高比表面积和高吸收特性，低细胞毒性的PPSNs可以有效地负载和保护pBMP-2。所构建的pPSN/pBMP-2能有效地转染MC3T3-E1细胞，促进成骨分化，增加体外钙沉积。有趣的是，由于自噬抑制剂的存在，钙沉积结节的质量减少，这表明PPSNs刺激了自噬途径。由于制备的PPSN/pBMP-2具有良好的生物相容性、高的转染率和刺激自噬的能力，可以在体内有效地转染缺损区的局部细胞。显微计算机断层扫描和组织学图像显示，PPSN/pBMP-2能够有效地促进5 mm大鼠颅骨缺损模型的新骨形成。综上所述，我们新合成的PPSNs可以有效地携带pBMP-2并将其运送到靶细胞，并刺激自噬途径，导致显著的成骨分化和骨再生。
Gene therapy is one of the most common and effective ways for the regeneration of defective bone tissue, but even highly efficient gene delivery vectors are insufficient. In this study, bone morphogenetic protein-2 plasmid (pBMP-2) was encapsulated by polyethylenimine-modified porous silica nanoparticles (PPSNs), which were synthesized via an ethyl ether emulsion method. Owing to the high specific surface area and high absorption characteristics, low cytotoxicy PPSNs can efficiently load and protect pBMP-2. The resulting PPSN/pBMP-2 can transfect MC3T3-E1 cells effectively to promote osteogenic differentiation and increase calcium deposition in vitro. Interestingly, the mass of calcium deposition nodules decreased dur to the presence of an autophagy inhibitor, demonstrating that PPSNs stimulated the autophagy pathway. Because of their excellent biocompatibility, high transfection efficiency, and ability to stimulate autophagy, the as-prepared PPSN/pBMP-2 could efficiently transfect local cells in a defect area in vivo. Micro-computed tomography and histological images demonstrated that PPSN/pBMP-2 could efficiently promote new bone formation in a 5 mm sized rat calvarial defect model. Taken together, our newly synthesized PPSNs could efficiently carry pBMP-2 and deliver it to the target cells as well as stimulating the autophagy pathway, resulting in significant osteogenic differentiation and bone regeneration.