Shramova E I, Deyev S M, Proshkina G M
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Academy of science, Moscow, 117997 Russian Federation.
Sechenov First Moscow State Medical University (Sechenov University), Moscow, 119991 Russian Federation.
Acta Naturae. 2024 Apr-Jun;16(2):72-81. doi: 10.32607/actanaturae.27425.
Today, in preclinical studies, optical bioimaging based on luminescence and fluorescence is indispensable in studying the development of neoplastic transformations, the proliferative activity of the tumor, its metastatic potential, as well as the therapeutic effect of antitumor agents. In order to expand the capabilities of optical imaging, sensors based on the bioluminescence resonance energy transfer (BRET) mechanism and, therefore, independent of an external light source are being developed. A targeted nanoplatform based on HER2-specific liposomes whose internal environment contains a genetically encoded BRET sensor was developed in this study to visualize deep-seated tumors characterized by overexpression of human epidermal growth factor receptor type 2 (HER2). The BRET sensor is a hybrid protein consisting of the highly catalytic luciferase NanoLuc (an energy donor) and a LSSmKate1 red fluorescent protein with a large Stokes shift (an energy acceptor). During the bioimaging of disseminated intraperitoneal tumors formed by HER2-positive SKOV3.ip1cells of serous ovarian cystadenocarcinoma, it was shown that the developed system is applicable in detecting deep-seated tumors of a certain molecular profile. The developed system can become an efficient platform for optimizing preclinical studies of novel targeted drugs.
如今,在临床前研究中,基于发光和荧光的光学生物成像对于研究肿瘤转化的发展、肿瘤的增殖活性、转移潜能以及抗肿瘤药物的治疗效果而言不可或缺。为了扩展光成像的能力,基于生物发光共振能量转移(BRET)机制且因此独立于外部光源的传感器正在被研发。在本研究中,开发了一种基于HER2特异性脂质体的靶向纳米平台,其内部环境包含一种基因编码的BRET传感器,以可视化以人表皮生长因子受体2型(HER2)过表达为特征的深部肿瘤。该BRET传感器是一种杂交蛋白,由高催化活性的纳米荧光素酶NanoLuc(能量供体)和具有大斯托克斯位移的红色荧光蛋白LSSmKate1(能量受体)组成。在对浆液性卵巢囊腺癌的HER2阳性SKOV3.ip1细胞形成的播散性腹膜内肿瘤进行生物成像期间,结果表明所开发的系统适用于检测具有特定分子特征的深部肿瘤。所开发的系统可以成为优化新型靶向药物临床前研究的有效平台。