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基于阿魏酸的三模态纳米装置抑制细胞内蛋白激酶 CK2。

Intracellular protein kinase CK2 inhibition by ferulic acid-based trimodal nanodevice.

机构信息

Department of Molecular Medicine, University of Pavia, via Forlanini 6, 27100 Pavia, Italy.

Department of Geosciences, University of Padova, via Gradenigo 6, 35131 Padova, Italy.

出版信息

Int J Biol Macromol. 2020 Dec 15;165(Pt A):701-712. doi: 10.1016/j.ijbiomac.2020.09.207. Epub 2020 Sep 30.

DOI:10.1016/j.ijbiomac.2020.09.207
PMID:33010276
Abstract

Protein kinase CK2, a pleiotropic and constitutively active kinase, is strictly involved in different diseases, especially in cancer. Many efforts have been carried out to develop specific CK2 inhibitors and recently, it has been evidenced that ferulic acid (FA) represents a promising, albeit cell impermeable, CK2 inhibitor. In the present study, the potential of a nanotechnological approach to cope with intracellular CK2 regulation was explored. Surface-Active Maghemite Nanoparticles (SAMNs), coupling magnetism with photoluminescence, a new feature of SAMNs here described for the first time, were chosen as dual imaging nanocarrier for FA. The self-assembled nanodevice (SAMN@FA) displayed a significant CK2 inhibitory activity in vitro. Moreover, effective cellular internalization of SAMN@FA in cancer cells was proved by direct visualization of the photoluminescent nanocarrier by confocal microscopy and was corroborated by phosphorylation levels of endogenous CK2 targets. The proposed trimodal nanodevice, representing the first example of cellular CK2 nano-inhibition, paves the way for novel active nanocarriers as appealing theranostic tool for future biomedical applications.

摘要

蛋白激酶 CK2 是一种多功能、组成型激活的激酶,与多种疾病,特别是癌症密切相关。为了开发特异性 CK2 抑制剂,已经进行了许多努力,最近有证据表明阿魏酸(FA)是一种有前途的、但细胞不可渗透的 CK2 抑制剂。在本研究中,探索了一种纳米技术方法来应对细胞内 CK2 调节。表面活性磁赤铁矿纳米粒子(SAMN)将磁性与光致发光相结合,SAMN 的这一新特性是首次在这里描述的,被选为 FA 的双模式成像纳米载体。自组装纳米器件(SAMN@FA)在体外显示出显著的 CK2 抑制活性。此外,通过共聚焦显微镜直接观察光致发光纳米载体,证明了 SAMN@FA 在癌细胞中的有效细胞内化,并且通过内源性 CK2 靶标磷酸化水平得到了证实。所提出的三模态纳米器件是细胞 CK2 纳米抑制的首例,为新型主动纳米载体铺平了道路,为未来的生物医学应用提供了有吸引力的治疗诊断工具。

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