Department of Biochemistry, Faculty of Science, Zanjan University, 45371-38791, Zanjan, Iran.
Nuclear Science & Technology Research Institute, Materials and Nuclear Fuel Research School, Tehran, 14395-836, Iran.
Anticancer Agents Med Chem. 2020;20(10):1250-1265. doi: 10.2174/1871520620666200220113452.
There is a significant dearth of clinical biochemistry researches to evaluate the facility of exploitation of folate targeted radioactive gold-labeled anti-cancer drugs against various cancer cell lines.
The aim of this paper was to develop a gold-based compound with an efficient therapeutic potential against breast cancer. To this end, the synthesis of the 198Au/PAMAM-MPEG-FA composite was considered here.
The radioactive gold (198Au) nanoparticles were encapsulated into Folic acid (FA)-targeted Polyamidoamine dendrimer (PAMAM) modified with Maleimide-Polyethylene glycol Succinimidyl Carboxymethyl ester (MPEG). After that, anticancer assessments of the prepared 198Au/PAMAM-MPEG-FA hybrid mater against breast cancer were investigated. Further studies were also devised to compare the anticancer capabilities of the 198Au/PAMAM-MPEG-FA composite with the synthesized P-MPEG, 197Au/P-MPEG, 197Au/P-MPEG-FA, 197Au/P-FA and 198Au/P-MPEG-FA conjugates. The prepared drugs were characterized by means of various analytical techniques. The radionuclidic purity of the 198Au/P-MPEG-FA solution was determined using High Purity Germanium (HPGe) spectroscopy and its stability in the presence of human serum was studied. The cell uptake and toxicity of the prepared drugs were evaluated in vitro, and some comparative studies of the toxicity of the drugs were conducted towards the MCF7 (Human breast cancer cell), 4T1 (Mice breast adenocarcinoma cell) and C2C12 (Mice muscle normal cell).
The results showed that cell uptake of 198Au/P-MPEG-FA nanoparticles is high in the 4T1 cell line and the order of uptake is as 4T1> MCF7> C2C12. Moreover, of the tested compounds, 198Au/P-MPEG-FA had the highest toxicity towards the cancerous 4T1 and MCF7 in all concentrations after 24, 48 and 72h (P < 0.001). Furthermore, the cytotoxicity of the drugs was concentration-dependent.
On the basis of the present research, 198Au/P-MPEG-FA has been proposed as a good candidate for the induction of cell death in breast cancer, although further experimental and clinical investigations are required.
目前，针对各种癌细胞系，评估叶酸靶向放射性金标记抗癌药物开发潜力的临床生化研究还很匮乏。
本研究旨在开发一种具有高效治疗潜力的基于金的化合物，用于治疗乳腺癌。为此，考虑合成金（198Au）/聚酰胺胺树枝状大分子（PAMAM）-聚乙二醇马来酰亚胺（MPEG）-叶酸（FA）复合材料。然后，评估了所制备的 198Au/PAMAM-MPEG-FA 杂化物对乳腺癌的抗癌作用。此外，还设计了进一步的研究来比较 198Au/PAMAM-MPEG-FA 复合材料与合成的 P-MPEG、197Au/P-MPEG、197Au/P-MPEG-FA、197Au/P-FA 和 198Au/P-MPEG-FA 缀合物的抗癌能力。采用各种分析技术对制备的药物进行了表征。通过高纯锗（HPGe）光谱法测定了 198Au/P-MPEG-FA 溶液的放射性核纯度，并研究了其在人血清中的稳定性。评估了制备药物的细胞摄取和毒性，并在体外进行了一些药物毒性的比较研究，对 MCF7（人乳腺癌细胞）、4T1（小鼠乳腺癌腺癌细胞）和 C2C12（小鼠肌肉正常细胞）进行了药物毒性的比较。
结果表明，198Au/P-MPEG-FA 纳米颗粒在 4T1 细胞系中的摄取率很高，摄取顺序为 4T1>MCF7>C2C12。此外，在所测试的化合物中，198Au/P-MPEG-FA 在所有浓度下对 24、48 和 72h 后具有最高的毒性，对癌症 4T1 和 MCF7 的毒性最高（P<0.001）。此外，药物的细胞毒性呈浓度依赖性。
基于本研究，198Au/P-MPEG-FA 被提出作为诱导乳腺癌细胞死亡的候选药物，尽管还需要进一步的实验和临床研究。
