Li Ziyu, Zhang Wenjing, Li Yongsheng, Yuan Yuan, Liu Changsheng
J Nanosci Nanotechnol. 2016 Jun;16(6):5528-36. doi: 10.1166/jnn.2016.11743.
Delivery of bone morphogenetic protein-2 (BMP-2) carries great promise for the field of bone regenerative medicine. But, how the size and curvature of matrix affect the way BMP-2 binding to the support and in turn influence its bioactivity remain poorly understood. In this contribution, silica nanoparticles (SNPs) with 20 nm, 60 nm and 100 nm (named as SNP20, SNP60, SNP100, respectively) were introduced as models. Based on the models, the nanoscale curvature-mediated adsorption dynamics, conformation, and bioactivity of recombinant human BMP-2 (rhBMP-2) were investigated. Our data showed that SNPs bound rapidly to and induced unfolding of rhBMP-2 molecules, which undermined their interactions with the corresponding receptors on the cell surface and decreased the bioactivities of adsorbed rhBMP-2. In contrast, rhBMP-2 showed increasingly stronger affinity to and lost less secondary structure on the larger SNPs, while better bioactivity was observed on the medium SNP60 surfaces. The results indicated that the size of the SNPs, perhaps because of the contribution of surface curvature, influences the structure and function of the adsorbed BMP-2. This study demonstrates the possibility to mediate the binding, conformation and bioactivity of BMP-2 by tailoring the nanoscale curvature, allowing fabrication of BMP-2-based bone tissue scaffolds with high osteoinductivity at low BMP-2 dosage.
骨形态发生蛋白-2（BMP-2）的递送在骨再生医学领域具有巨大的前景。但是，基质的大小和曲率如何影响BMP-2与载体的结合方式，进而影响其生物活性，目前仍知之甚少。在本研究中，引入了粒径分别为20 nm、60 nm和100 nm的二氧化硅纳米颗粒（分别命名为SNP20、SNP60、SNP100）作为模型。基于这些模型，研究了重组人BMP-2（rhBMP-2）的纳米级曲率介导的吸附动力学、构象和生物活性。我们的数据表明，SNP能迅速与rhBMP-2分子结合并诱导其展开，这破坏了它们与细胞表面相应受体的相互作用，并降低了吸附的rhBMP-2的生物活性。相比之下，rhBMP-2在较大的SNP上表现出越来越强的亲和力，且二级结构损失较少，而在中等大小的SNP60表面观察到更好的生物活性。结果表明，SNP的大小可能由于表面曲率的作用，影响了吸附的BMP-2的结构和功能。本研究证明了通过调整纳米级曲率来介导BMP-2的结合、构象和生物活性的可能性，从而能够在低BMP-2剂量下制造具有高骨诱导性的基于BMP-2的骨组织支架。
