镉纳米簇作为安全纳米载体:BALB/c 小鼠体内的生物分布以及将藏红花素携带至乳腺癌细胞系的应用。
Cadmium nanocluster as a safe nanocarrier: biodistribution in BALB/c mice and application to carry crocin to breast cancer cell lines.
发表日期:2024
作者:
Moslem Jafarisani, S Ali Hashemi, Nassim Faridi, Mir F Mousavi, S Zahra Bathaie
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
金属纳米团簇是适用于药物输送的新兴纳米材料。在此,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,将其用于乳腺癌细胞系中的靶向药物递送。采用绿色化学路线,基于牛血清白蛋白合成了镉纳米簇(Cd-NC)。表征后,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)结合。研究了透明质酸化镉-CN (HA-Cd-NC) 负载和释放藏红花素 (Cro)(一种抗癌植物化学物质)的效率。最后,将其应用于一组乳腺癌细胞系的细胞死亡诱导。彗星试验结果表明,与Cd2和高锰酸钾(KMnO4)不同,Cd-NC在体外不会诱导遗传毒性和氧化应激。然后,研究了这种 Cd-NC 的体内药代动力学。数据显示,Cd-NC已在小鼠肝脏中积累,并从小鼠粪便中排出。与 Cd2 不同,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 HA(CD44 细胞表面受体的配体),将 Cd-NC 靶向乳腺癌细胞。之后,将 Cro 负载到 HA-Cd-NC 上,用于治疗一组具有不同程度 CD44 的人类乳腺癌细胞系。当Cro负载在HA-Cd-NC上时,半数最大药物抑制浓度(IC50)显着降低,特别是在表面CD44程度较高的MDA-MB-468上。这些结果表明,当通过 HA-Cd-NC 进行时,Cro 对乳腺癌具有更高的毒性。Cd-NC 是完全安全的,并且是向目标乳腺肿瘤输送抗癌药物/植物化学物质的有前途的候选者。© 作者)2024 年。
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.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.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.The Cd-NC was completely safe and is a promising candidate for delivering anticancer drugs/phytochemicals into the targeted breast tumors.© The Author(s) 2024.