纳米镉簇作为一种安全的纳米载体:在 BALB/c 小鼠体内的生物分布以及在乳腺癌细胞系中携带巴豆毒素的应用。

Q3 Medicine
Exploration of targeted anti-tumor therapy Pub Date : 2024-01-01 Epub Date: 2024-05-28 DOI:10.37349/etat.2024.00233
Moslem Jafarisani, S Ali Hashemi, Nassim Faridi, Mir F Mousavi, S Zahra Bathaie
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引用次数: 0

摘要

目的:金属纳米簇是一种可用于给药的新兴纳米材料。本文比较了二价阳离子镉(Cd2+)与纳米簇形式的镉的毒性和氧化应激诱导作用。然后将其用于乳腺癌细胞系的靶向给药:方法:采用绿色化学方法,在牛血清白蛋白的基础上合成了镉纳米团簇(Cd-NC)。方法:采用绿色化学方法,在牛血清白蛋白的基础上合成了一种镉纳米团簇(Cd-NC),并在体外和体内对其遗传毒性和氧化应激诱导进行了研究。之后,将其与透明质酸(HA)共轭。研究了透明质酸化-Cd-CN(HA-Cd-NC)负载和释放抗癌植物化学物 crocin(Cro)的效率。最后,将其用于诱导乳腺癌细胞系的细胞死亡:彗星试验结果表明,与 Cd2+ 和高锰酸钾(KMnO4)不同,Cd-NC 在体外不会诱导基因毒性和氧化应激。然后,研究了 Cd-NC 在体内的药代动力学。数据显示,Cd-NC 在小鼠肝脏中蓄积,并从粪便中排出。与 Cd2+ 不同的是,这种 Cd-NC 在动物组织中不会引起毒性和氧化应激。然后,通过添加 CD44 细胞表面受体的配体 HA,将 Cd-NC 靶向乳腺癌细胞。然后,在 HA-Cd-NC 上载入 Cro,并将其用于治疗具有不同程度 CD44 的人类乳腺癌细胞系。当Cro负载在HA-CD-NC上时,其半最大药物抑制浓度(IC50)明显降低,尤其是在表面CD44程度较高的MDA-MB-468中。这些结果表明,当使用 HA-Cd-NC 时,Cro 对乳腺癌的毒性更高:结论:Cd-NC 完全安全,是向目标乳腺肿瘤递送抗癌药物/植物化学物质的理想候选材料。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cadmium nanocluster as a safe nanocarrier: biodistribution in BALB/c mice and application to carry crocin to breast cancer cell lines.

Aim: Metal nanoclusters are emerging nanomaterials applicable for drug delivery. Here, the toxicity and oxidative stress induction of divalent cationic cadmium (Cd2+) was compared with a Cd in the form of nanocluster. Then, it was used for targeted drug delivery into breast cancer cell lines.

Methods: Using a green chemistry route, a Cd nanocluster (Cd-NC) was synthesized based on bovine serum albumin. After characterization, its genotoxicity and oxidative stress induction were studied in both in vitro and in vivo. After that, it was conjugated with hyaluronic acid (HA). The efficiency of hyaloronized-Cd-CN (HA-Cd-NC) for loading and releasing crocin (Cro), an anticancer phytochemical, was studied. Finally, it was applied for cell death induction in a panel of breast cancer cell lines.

Results: The comet assay results indicated that, unlike Cd2+ and potassium permanganate (KMnO4), no genotoxicity and oxidative stress was induced by Cd-NC in vitro. Then, the pharmacokinetics of this Cd-NC was studied in vivo. The data showed that Cd-NC has accumulated in the liver and excreted from the feces of mice. Unlike Cd2+, no toxicity and oxidative stress were induced by this Cd-NC in animal tissues. Then, the Cd-NC was targeted toward breast cancer cells by adding HA, a ligand for the CD44 cell surface receptor. After that, Cro was loaded on HA-Cd-NC and it was used for the treatment of a panel of human breast cancer cell lines with varying degrees of CD44. The half-maximal drug inhibitory concentration (IC50) of Cro was significantly decreased when it was loaded on HA-Cd-NC, especially in MDA-MB-468 with a higher degree of CD44 at the surface. These results indicate the higher toxicity of Cro toward breast cancers when carried out by HA-Cd-NC.

Conclusions: The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.

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