多柔比星的双载体磷脂纳米系统:在体外乳腺癌细胞中的积累和细胞毒性作用。

Q3 Biochemistry, Genetics and Molecular Biology
Yu A Tereshkina, F N Bedretdinov, L V Kostryukova
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引用次数: 0

摘要

各种化疗药物被用于治疗乳腺癌(BC),其中一种是蒽环类抗生素多柔比星(Dox),它除了具有细胞抑制作用外,还有严重的副作用。为了减少其对健康器官和组织的负面影响,并增加其在肿瘤中的蓄积,Dox 被纳入磷脂纳米颗粒中。由于活性物质在肿瘤组织中的蓄积量较高,因此额外使用载体分子对特定靶点进行靶向递送可提高 Dox 的疗效。本研究将在癌症血管生成中发挥重要作用的整合素αvβ3和负责细胞分化和增殖的叶酸受体视为此类载体分子的靶点。因此,制备了一种含有两种载体配体(cRGD 肽和叶酸)的 Dox 磷脂组合物(NPh-Dox-cRGD-Fol(3,4))。对所制备组合物 NPh-Dox-cRGD-Fol(3,4) 的物理性质研究表明,其平均粒径为 39.62±4.61 nm,ζ电位值为 4.17±0.83 mV。几乎所有的 Dox 分子都与磷脂纳米颗粒结合(99.85±0.21%)。与分别含有两种载体(叶酸或 cRGD 肽)的组合物相比,同时使用两种载体可使 MDA-MB-231 BC 细胞中的 Dox 积累增加近 20%。此外,与单独使用叶酸和 cRGD 肽的情况相比,Dox 的内化程度分别高出 22% 和 24%。在将含有叶酸的组合物作为单一载体(NPh-Dox-Fol(3,4))和与 RGD 肽(NPh-Dox-cRGD-Fol(3,4))一起培养时,对 MDA-MB-231 细胞的细胞毒作用更高。在 Wi-38 二倍体成纤维细胞系上进行的实验表明,与游离 Dox 相比,无论磷脂成分中是否含有载体分子,其细胞毒性作用都明显较低。研究结果表明,在一种磷脂组合物中使用两种载体来靶向输送 Dox 是有潜力的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A dual-vector phospholipid nanosystem of doxorubicin: accumulation and cytotoxic effect in breast cancer cells in vitro.

Various chemotherapeutic agents are used to treat breast cancer (BC); one of them is the anthracycline antibiotic doxorubicin (Dox), which, in addition to its cytostatic effect, has serious side effects. In order to reduce its negative impact on healthy organs and tissues and to increase its accumulation in tumors, Dox was incorporated into phospholipid nanoparticles. The additional use of vector molecules for targeted delivery to specific targets can increase the effectiveness of Dox due to higher accumulation of the active substance in the tumor tissue. The integrin αvβ3, which plays an important role in cancer angiogenesis, and the folic acid receptor, which is responsible for cell differentiation and proliferation, have been considered in this study as targets for such vector molecules. Thus, a phospholipid composition of Dox containing two vector ligands, cRGD peptide and folic acid (NPh-Dox-cRGD-Fol(3,4)), was prepared. Study of the physical properties of the developed composition NPh-Dox-cRGD-Fol(3,4) showed that the average particle size was 39.62±4.61 nm, the ζ-potential value was 4.17±0.83 mV. Almost all Dox molecules were incorporated into phospholipid nanoparticles (99.85±0.21%). The simultaneous use of two vectors in the composition led to an increase in the Dox accumulation in MDA-MB-231 BC cells by almost 20% as compared to compositions containing each vector separately (folic acid or the cRGD peptide). Moreover, the degree of Dox internalization was 22% and 24% higher than in the case of separate use of folic acid and cRGD peptide, respectively. The cytotoxic effect on MDA-MB-231 cells was higher during incubations with the compositions containing folic acid as a single vector (NPh-Dox-Fol(3,4)) and together with the RGD peptide (NPh-Dox-cRGD-Fol(3,4)). Experiments on the Wi-38 diploid fibroblast cell line have shown a significantly lower degree of cytotoxic effect of the phospholipid composition, regardless of the presence of the vector molecules in it, as compared to free Dox. The results obtained indicate the potential of using two vectors in one phospholipid composition for targeted delivery of Dox.

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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍: The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).
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