State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Victoria 3052, Australia.
Spectrochim Acta A Mol Biomol Spectrosc. 2022 Mar 15;269:120736. doi: 10.1016/j.saa.2021.120736. Epub 2021 Dec 10.
Photothermal therapy is one of the promising approaches toward cancer treatment. To date, several compounds have been developed for this application, among which nanoparticles are attracting ever-increasing attention. One of the obstacles in developing efficient photothermal nanoparticle agents is their off-target effect which is mainly mediated via non-specific interactions with proteins. Such interaction not only reduces the bioavailability of the agent but also will cause protein aggregation that can be lethal. So, gaining knowledge on the mechanisms mediating such interactions will facilitate development of more effective agents. Our last studies showed the mechanism of action of two modified gold nanoparticles, folic acid functionalized gold nanoparticles (FA-AuNPs) and gold shelled FeO nanoparticles (AuFeNPs), as photothermal agents. In the current work, we focus on the interaction of these two NPs with human serum albumin (HSA) and human hemoglobin (Hb) as model proteins. The complex formation between NPs and proteins was investigated by fluorescence spectroscopy, dynamic light scattering and circular dichroism. Our data distinguishes the very distinct mode of interaction of charged and neutral NPs with proteins. While the interaction of neutral AuFeNP to proteins is protein dependent, charged nanoparticles FA-AuNP interact indistinguishably with all proteins via electrostatic interactions. Moreover, complexes obtained from FA-AuNPs with proteins are more stable than that of AuFeNP. However, the secondary structure content of proteins in the presence of NPs indicates the insignificant effect of NPs on the secondary structure of these proteins. Our data propose that the charge functionalization of the NPs is an effective way for modulating the interaction of nanoparticles with proteins.
光热疗法是癌症治疗的一种很有前途的方法。迄今为止，已经开发了几种用于该应用的化合物，其中纳米颗粒越来越受到关注。开发高效光热纳米颗粒剂的障碍之一是其非靶向效应，主要通过与蛋白质的非特异性相互作用介导。这种相互作用不仅降低了试剂的生物利用度，而且还会导致蛋白质聚集，从而可能致命。因此，了解介导这种相互作用的机制将有助于开发更有效的试剂。我们的最新研究表明了两种修饰金纳米颗粒（叶酸功能化金纳米颗粒（FA-AuNPs）和金壳 FeO 纳米颗粒（AuFeNPs）作为光热试剂的作用机制。在目前的工作中，我们专注于这两种 NPs 与人血清白蛋白（HSA）和人血红蛋白（Hb）作为模型蛋白的相互作用。通过荧光光谱、动态光散射和圆二色性研究了 NPs 与蛋白质之间的复合物形成。我们的数据区分了带电荷和不带电荷的 NPs 与蛋白质相互作用的非常不同模式。虽然中性 AuFeNP 与蛋白质的相互作用是蛋白质依赖性的，但带电荷的纳米粒子 FA-AuNP 通过静电相互作用与所有蛋白质无区别地相互作用。此外，与 FA-AuNPs 从蛋白质获得的复合物比 AuFeNP 更稳定。然而，存在 NPs 时蛋白质的二级结构含量表明 NPs 对这些蛋白质的二级结构的影响不大。我们的数据表明， NPs 的电荷功能化是调节 NPs 与蛋白质相互作用的有效方法。
