关键词: CD44 Cadmium nanocluster antioxidant enzymes breast cancer cell line hyaluronic acid oxidative stress

来  源:   DOI:10.37349/etat.2024.00233   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.
摘要:
金属纳米团簇是适用于药物递送的新兴纳米材料。这里,将二价阳离子镉(Cd2)的毒性和氧化应激诱导与纳米簇形式的Cd进行了比较。然后,它被用于靶向药物递送到乳腺癌细胞系中。
使用绿色化学路线,以牛血清白蛋白为原料合成了Cd纳米簇(Cd-NC)。在表征之后,在体外和体内研究了其遗传毒性和氧化应激诱导。之后,它与透明质酸(HA)缀合。透明质化Cd-CN(HA-Cd-NC)装载和释放藏红花素(Cro)的效率,一种抗癌植物化学物质,被研究过。最后,它被应用于一组乳腺癌细胞系的细胞死亡诱导。
彗星测定结果表明,与Cd2+和高锰酸钾(KMnO4)不同,Cd-NC在体外无遗传毒性和氧化应激。然后,在体内研究了这种Cd-NC的药代动力学。数据显示,Cd-NC已在肝脏中积累并从小鼠的粪便中排出。与Cd2+不同,这种Cd-NC在动物组织中没有毒性和氧化应激。然后,Cd-NC通过添加HA靶向乳腺癌细胞,CD44细胞表面受体的配体。之后,将Cro加载到HA-Cd-NC上,并将其用于治疗一组具有不同程度CD44的人乳腺癌细胞系。当Cro负载于HA-Cd-NC时,其半数最大药物抑制浓度(IC50)显著降低,特别是在表面具有更高程度的CD44的MDA-MB-468中。这些结果表明,当通过HA-Cd-NC进行时,Cro对乳腺癌的毒性更高。
Cd-NC是完全安全的,并且是将抗癌药物/植物化学物质递送到靶向乳腺肿瘤中的有希望的候选者。
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