Cucci Lorena Maria, Trapani Giuseppe, Hansson Örjan, La Mendola Diego, Satriano Cristina
Laboratory of Hybrid NanoBioInterfaces (NHBIL), Department of Chemical Sciences, University of Catania, 95125 Catania, Italy.
Scuola Superiore di Catania, University of Catania, 95123 Catania, Italy.
Nanomaterials (Basel). 2021 Jan 14;11(1):201. doi: 10.3390/nano11010201.
In this work, we aimed to develop a hybrid theranostic nano-formulation based on gold nanoparticles (AuNP)-having a known anti-angiogenic character-and the angiogenin (ANG), in order to tune the angiogenesis-related phases involved in the multifaceted process of the wound healing. To this purpose, spherical were surface "decorated" with three variants of the protein, namely, the recombinant (rANG), the wild-type, physiologically present in the human plasma (wtANG) and a new mutant with a cysteine substitution of the serine at the residue 28 (S28CANG). The hybrid biointerface between AuNP and ANG was scrutinized by a multi-technique approach based on dynamic light scattering, spectroscopic (UV-visible, circular dichroism) and microscopic (atomic force and laser scanning confocal) techniques. The analyses of optical features of plasmonic gold nanoparticles allowed for discrimination of different adsorption modes-i.e.; predominant physisorption and/or chemisorption-triggered by the ANG primary sequence. Biophysical experiments with supported lipid bilayers (SLB), an artificial model of cell membrane, were performed by means of quartz crystal microbalance with dissipation monitoring acoustic sensing technique. Cellular experiments on human umbilical vein endothelial cells (HUVEC), in the absence or presence of copper-another co-player of angiogenesis-were carried out to assay the nanotoxicity of the hybrid protein-gold nanoassemblies as well as their effect on cell migration and tubulogenesis. Results pointed to the promising potential of these nanoplatforms, especially the new hybrid Au-S28CANG obtained with the covalent grafting of the mutant on the gold surface, for the modulation of angiogenesis processes in wound care.
在本研究中,我们旨在开发一种基于具有已知抗血管生成特性的金纳米颗粒(AuNP)和血管生成素(ANG)的混合诊疗纳米制剂,以调节伤口愈合多方面过程中涉及的血管生成相关阶段。为此,用该蛋白的三种变体对球形颗粒进行表面“修饰”,即重组体(rANG)、生理上存在于人体血浆中的野生型(wtANG)以及在第28位残基处丝氨酸被半胱氨酸取代的新突变体(S28CANG)。基于动态光散射、光谱(紫外可见、圆二色)和显微镜(原子力和激光扫描共聚焦)技术的多技术方法对AuNP和ANG之间的混合生物界面进行了研究。对等离子体金纳米颗粒光学特性的分析有助于区分由ANG一级序列引发的不同吸附模式,即主要的物理吸附和/或化学吸附。通过带有耗散监测声学传感技术的石英晶体微天平对细胞膜的人工模型——支持脂质双层(SLB)进行了生物物理实验。在有无铜(血管生成的另一个协同因子)存在的情况下,对人脐静脉内皮细胞(HUVEC)进行细胞实验,以测定混合蛋白-金纳米组装体的纳米毒性及其对细胞迁移和管形成的影响。结果表明,这些纳米平台具有广阔的应用前景,特别是通过将突变体共价接枝到金表面获得的新型混合Au-S28CANG,在伤口护理中对血管生成过程具有调节作用。