中文摘要
纳米材料与蛋白质的相互作用是理解工程化的纳米材料复杂而多变的生物学效应及其生物安全性的关键因素。富勒烯C60及其衍生物作为一类经典的工程类材料由于其独特的生物学活性现如今已成为许多疾病潜在的治疗药物,在生物医药领域具有非常广泛的应用潜力。但关于富勒烯C60通过调整与其相互作用的蛋白的结构和功能从而发挥其生物学效应的研究还很少。本项目前期工作显示富勒烯C60纳米晶体能够与CaMKIIδ特异性相互作用,并氧化激活心脏中的CaMKIIδ,产生激酶活性依赖的心脏毒性。在前期工作基础上,本项目进一步研究二者相互作用的结构基础及相关规律,揭示富勒烯C60纳米晶体对CaMKIIδ活性的影响及其产生的下游一系列心脏毒性效应的分子机制,为富勒烯C60生物安全性的评估提供理论依据和研究方法,也为其在体内更广泛的应用开发了新的突破口。
英文摘要
Nanoparticle-protein interactions hold one of the keys for understanding the diverse and oftentimes unexpected biological effects and bio-safty elicited by engineered nanomaterials. Buckminster fullerene C60 and its derivatives as a classic engineered nanomaterial are currently being actively pursued as potential therapeutic agents for many human diseases and are widely used in the field of biomedicine owing to their outstanding biological activities. However, few studies have carefully addressed the potential biological consequences of fullerene C60 through structural and functional modulation of interacting proteins. Our previous work has demonstrated the interaction between fullerene C60 and CaMKIIδ. Fullerene C60 has the capacity to induce oxidation of kinase and lead to the cardiac toxicity of rat in a CaMKIIδ dependent manner. The proposing project will focus on the structural basis on fullerene C60-CaMKIIδ interactions in order to clarify the activation modulation of CaMKIIδ and a series downstream biological effects on cardiac toxicity elicited by fullerene C60.The further investigation of this project will provide theoretical basis and research method for bio-safety assessment, and also make a novel breakthrough for a wider and more precise application of fullerene C60 in vivo.
