Yang Bin, Jia Rui, Fang Mengke, Wang Siyi, Lv Zhe, Wang Jing
Department of Environmental Science and Engineering, School of Environmental and Material Engineering, Yantai University, 30# Qingquan Road, Yantai 264005, P. R. China.
Polymer Materials and Engineering, School of Engineering, Queen Mary University of London, Northwestern Polytechnical University, 1# Dongxiang Road, Xi 'an 710129, P. R. China.
Toxicol Res (Camb). 2022 Jul 14;11(4):654-661. doi: 10.1093/toxres/tfac044. eCollection 2022 Aug.
Although superparamagnetic iron oxide nanoparticles (SPIONs) are used as carriers for lipase (CRL) in biomedical fields, their interactions and the influences on CRL are still unknown. Consequently, SPIONs were synthesized, characterized, and incubated with CRL to explore their molecular interactions and interacting consequences in this study.
The toxic effects of SPIONs on CRL and their molecular interactions were explored through transmission electron microscope, isothermal titration calorimetry, zeta potential measurements, multi-spectroscopic techniques, and biological enzyme activity tests.
Results revealed the adsorption of SPIONs to CRL and the reduction of CRL aggregation. The unfolding and loosening of CRL structure as well as the change of secondary structure with the decrease of α-helix were found under SPIONs exposure. Moreover, higher SPIONs concentrations contributed to larger conformational changes and less aggregation of CRL. Meanwhile, it showed that hydrophobic forces were the dominant driving forces in the binding process, with the participation of electrostatic forces. CRL binds to SPIONs with the stoichiometry of 20.7 and the binding constant of 9.9 × 10 M. No obvious changes were found in CRL activity due to no interference to Ser-209, Glu-341, and His-449 residues.
This study examined the biological compatibility of SPIONs at the molecular level and provided important information about the structure and function of CRL upon binding to SPIONs. Our work might contribute to comprehend the molecular toxicity of SPIONs and the risks of engineered nanoparticles to human health.
尽管超顺磁性氧化铁纳米颗粒(SPIONs)在生物医学领域被用作脂肪酶(CRL)的载体,但其相互作用以及对CRL的影响仍不清楚。因此,本研究合成、表征了SPIONs,并将其与CRL一起孵育,以探索它们的分子相互作用及相互作用结果。
通过透射电子显微镜、等温滴定量热法、zeta电位测量、多光谱技术和生物酶活性测试,探索了SPIONs对CRL的毒性作用及其分子相互作用。
结果揭示了SPIONs对CRL的吸附以及CRL聚集的减少。在SPIONs存在下,发现CRL结构展开和松弛,以及随着α-螺旋减少二级结构发生变化。此外,更高浓度的SPIONs导致CRL更大的构象变化和更少的聚集。同时,结果表明疏水作用力是结合过程中的主要驱动力,静电作用力也参与其中。CRL与SPIONs以化学计量比20.7结合,结合常数为9.9×10 M。由于对Ser-209、Glu-341和His-449残基无干扰,CRL活性未发现明显变化。
本研究在分子水平上研究了SPIONs的生物相容性,并提供了有关CRL与SPIONs结合后结构和功能的重要信息。我们的工作可能有助于理解SPIONs的分子毒性以及工程纳米颗粒对人类健康的风险。