School of Physics and Astronomy, Faculty of Engineering and Physical Sciences, University of Leeds, Leeds, UK.
ISIS Neutron and Muon Spallation Source, STFC Rutherford Appleton Laboratory, Oxfordshire, UK.
Biomater Sci. 2023 Apr 11;11(8):2726-2737. doi: 10.1039/d2bm01918c.
Globular folded proteins are powerful building blocks to create biomaterials with mechanical robustness and inherent biological functionality. Here we explore their potential as advanced drug delivery scaffolds, by embedding microbubbles (MBs) within a photo-activated, chemically cross-linked bovine serum albumin (BSA) protein network. Using a combination of circular dichroism (CD), rheology, small angle neutron scattering (SANS) and microscopy we determine the nanoscale and mesoscale structure and mechanics of this novel multi-composite system. Optical and confocal microscopy confirms the presence of MBs within the protein hydrogel, their reduced diffusion and their effective rupture using ultrasound, a requirement for burst drug release. CD confirms that the inclusion of MBs does not impact the proportion of folded proteins within the cross-linked protein network. Rheological characterisation demonstrates that the mechanics of the BSA hydrogels is reduced in the presence of MBs. Furthermore, SANS reveals that embedding MBs in the protein hydrogel network results in a smaller number of clusters that are larger in size (∼16.6% reduction in number of clusters, 17.4% increase in cluster size). Taken together, we show that MBs can be successfully embedded within a folded protein network and ruptured upon application of ultrasound. The fundamental insight into the impact of embedded MBs in protein scaffolds at the nanoscale and mesoscale is important in the development of future platforms for targeted and controlled drug delivery applications.
球状折叠蛋白是构建具有机械强度和固有生物功能的生物材料的有力构建块。在这里，我们通过在光激活的、化学交联的牛血清白蛋白 (BSA) 蛋白网络中嵌入微泡 (MB) 来探索它们作为先进药物输送支架的潜力。我们使用圆二色性 (CD)、流变学、小角中子散射 (SANS) 和显微镜相结合的方法来确定这种新型多复合材料系统的纳米和介观结构和力学性质。光学和共焦显微镜证实了 MB 存在于蛋白质水凝胶中，它们的扩散减少，并且可以使用超声有效破裂，这是爆发式药物释放的要求。CD 证实，MB 的包含不会影响交联蛋白网络中折叠蛋白的比例。流变特性表明，在存在 MB 的情况下，BSA 水凝胶的力学性能降低。此外，SANS 表明，将 MB 嵌入蛋白质水凝胶网络中会导致较小数量的簇，且尺寸较大（簇的数量减少约 16.6%，簇的尺寸增加 17.4%）。总之，我们表明，MB 可以成功地嵌入折叠蛋白网络中，并在应用超声时破裂。在纳米和介观尺度上嵌入 MB 对蛋白质支架的影响的基本见解对于开发用于靶向和控制药物输送应用的未来平台非常重要。
