Varlamova Elena G, Gudkov Sergey V, Blinova Ekaterina V, Blinov Dmitrii S, Turovsky Egor A
Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", 142290, Pushchino, Russia.
Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilove st., 119991, Moscow, Russia.
Biochem Biophys Res Commun. 2025 Jul 8;769:151962. doi: 10.1016/j.bbrc.2025.151962. Epub 2025 May 7.
Despite significant advances in the treatment of colon cancer, this disease is extremely common, often requiring serious surgery followed by long-term drug treatment. Colon and rectal cancer remain dangerous forms of cancer due to the high degree of metastasis. The development and study of the effectiveness of anticancer drugs based on nanoparticles is an urgent task of modern biomedicine. Of particular interest are attempts to move research from the in vitro level to the in vivo level of preclinical studies. In the presented study, mice were subcutaneously implanted with MC-38 cell line, a tumor was grown, and selenium nanoparticles (SeNPs) with a diameter of 100 nm obtained using the laser ablation method were administered intraperitoneally. Using morphometric measurements, it was found that injections of 1 μg/g or 10 μg/g SeNPs inhibited weight loss of mice during cancer development, reduced tumor size by 2-2.5 times, and suppressed metastasis by 1.5-3 times. Analysis of selenium levels in mouse blood, liver and tumor samples by atomic absorption spectrometry after the end of SeNPs treatment showed that the nanoparticles increased selenium levels in the blood and liver of mice without a significant dose-dependence, whereas in tumors a dose-dependent increase in selenium concentration was detected from the concentration of nanoparticles, with 10 μg/g SeNPs causing a more pronounced increase in selenium concentration. Using PCR and Western blot analysis, it was possible to establish that SeNPs injections led to an increase in the expression of genes encoding anti-inflammatory and anti-hypoxic proteins, but reduced the expression of antioxidant selenium-containing proteins and proteins responsible for the proliferation of cancer cells. Both concentrations of SeNPs led to similar effects, but increasing the concentration of nanoselenium to 10 μg/g affected the expression of a larger number of genes and the effects on expression were more "bright". Thus, the complex of presented experiments showed that injections of selenium nanoparticles in concentrations of 1 μg/g or 10 μg/g are capable to transport by the bloodstream and accumulating in the highest concentration in colon adenocarcinoma, compared with liver, which indicates the targeting of SeNPs in relation to tumors even without functionalization by specific molecules. As a result, there was a change in the expression patterns of genes and a number of proteins, and as a result, there was a decrease in tumor volume, normalization of mouse weight and maintenance of positive dynamics throughout the entire observation period.
尽管结肠癌治疗取得了重大进展,但这种疾病极为常见,通常需要进行大手术,随后进行长期药物治疗。由于转移程度高,结肠癌和直肠癌仍然是危险的癌症形式。基于纳米颗粒的抗癌药物的开发和有效性研究是现代生物医学的一项紧迫任务。特别令人感兴趣的是将研究从体外水平推进到临床前研究的体内水平的尝试。在本研究中,将MC-38细胞系皮下植入小鼠体内,使其长出肿瘤,然后将通过激光烧蚀法获得的直径为100纳米的硒纳米颗粒经腹腔注射给药。通过形态测量发现,注射1μg/g或10μg/g的硒纳米颗粒可抑制小鼠在癌症发展过程中的体重减轻,使肿瘤大小缩小2至2.5倍,并将转移抑制1.5至3倍。在硒纳米颗粒治疗结束后,通过原子吸收光谱法分析小鼠血液、肝脏和肿瘤样本中的硒水平,结果表明纳米颗粒使小鼠血液和肝脏中的硒水平升高,且无明显剂量依赖性,而在肿瘤中,从纳米颗粒浓度可检测到硒浓度呈剂量依赖性增加,10μg/g的硒纳米颗粒使硒浓度升高更为明显。通过PCR和蛋白质印迹分析,可以确定注射硒纳米颗粒导致编码抗炎和抗缺氧蛋白的基因表达增加,但降低了含抗氧化硒蛋白和负责癌细胞增殖的蛋白的表达。两种浓度的硒纳米颗粒都产生了类似的效果,但将纳米硒浓度提高到10μg/g会影响更多基因的表达,且对表达的影响更为“明显”。因此,所进行的一系列实验表明,注射浓度为1μg/g或10μg/g的硒纳米颗粒能够通过血液循环运输,并在结肠腺癌中以最高浓度积累,与肝脏相比,这表明即使没有特定分子功能化,硒纳米颗粒也具有针对肿瘤的靶向性。结果,基因和多种蛋白质的表达模式发生了变化,进而肿瘤体积减小,小鼠体重恢复正常,并在整个观察期内保持积极的变化趋势。