Kostryukova Lyubov V, Serdyukova Anastasia S, Pronina Veronica V, Shumyantseva Victoria V, Tereshkina Yulia A
Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia.
Pharmaceutics. 2024 Nov 2;16(11):1412. doi: 10.3390/pharmaceutics16111412.
The main aim of our experiments was to demonstrate the suitability of cell-based biosensors for searching for new anticancer medicinal preparations. The effect of the substance doxorubicin, doxorubicin embedded in phospholipid nanoparticles, and doxorubicin with phospholipid nanoparticles modified by targeting vectors (cRGD and folic acid) on dsDNA and breast cancer cell lines (MCF-7, MDA-MB-231) was studied. In the obtained doxorubicin nanoforms, the particle size was less than 60 nm. Our study of the percentage of doxorubicin inclusion showed the almost complete embeddability of the substance into nanoparticles for all samples, with an average of 95.4 ± 4.6%. The calculation of the toxicity index of the studied doxorubicin samples showed that all substances were moderately toxic drugs in terms of adenine and guanine. The biosensor analysis using electrodes modified with carbon nanotubes showed an intercalation interaction between doxorubicin and its derivatives and dsDNA, except for the composition of doxorubicin with folic acid with a linker length of 2000 (NPh-Dox-Fol(2.0)). The results of the electroanalysis were normalized to the total cell protein (mg) and cell concentration. The highest intensity of the electrochemical signals was observed in intact control cells of the MCF-7 and MDA-MB-231 cell lines. The proposed electrochemical approach is useful for the analysis of cell line responses to the medicinal preparations.
我们实验的主要目的是证明基于细胞的生物传感器在寻找新型抗癌药物制剂方面的适用性。研究了阿霉素、嵌入磷脂纳米颗粒的阿霉素以及经靶向载体（cRGD和叶酸）修饰的含磷脂纳米颗粒的阿霉素对双链DNA和乳腺癌细胞系（MCF-7、MDA-MB-231）的影响。在所获得的阿霉素纳米形式中，粒径小于60nm。我们对阿霉素包封率的研究表明，所有样品中该物质几乎都能完全嵌入纳米颗粒，平均包封率为95.4±4.6%。对所研究的阿霉素样品毒性指数的计算表明，就腺嘌呤和鸟嘌呤而言，所有物质均为中度毒性药物。使用碳纳米管修饰电极的生物传感器分析表明，除了连接子长度为2000的含叶酸阿霉素组合物（NPh-Dox-Fol(2.0)）外，阿霉素及其衍生物与双链DNA之间存在嵌入相互作用。电分析结果以总细胞蛋白（mg）和细胞浓度进行归一化。在MCF-7和MDA-MB-231细胞系的完整对照细胞中观察到最高强度的电化学信号。所提出的电化学方法可用于分析细胞系对药物制剂的反应。
