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新型 pH 响应性海藻酸钠稳定的姜黄素-硒-ZIF-8 纳米复合材料用于协同乳腺癌治疗。

Novel pH-responsive alginate-stabilized curcumin-selenium-ZIF-8 nanocomposites for synergistic breast cancer therapy.

机构信息

Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.

出版信息

J Drug Target. 2024 Apr;32(4):444-455. doi: 10.1080/1061186X.2024.2324935. Epub 2024 Mar 7.

DOI:10.1080/1061186X.2024.2324935
PMID:38445558
Abstract

In this study, a novel selenium@zeolitic imidazolate framework core/shell nanocomposite stabilised with alginate was used to improve the anti-tumour activity of curcumin. The developed alginate-stabilised curcumin-loaded selenium@zeolitic imidazolate framework (Alg@Cur@Se@ZIF-8) had a mean diameter of 159.6 nm and polydispersity index < 0.25. The release of curcumin from the nanocarrier at pH 5.4 was 2.69 folds as high as at pH 7.4. The bare nanoparticles showed haemolytic activity of about 12.16% at a concentration of 500 µg/mL while covering their surface with alginate reduced this value to 5.2%. By investigating cell viability, it was found that Alg@Cur@Se@ZIF-8 caused more cell death than pure curcumin. Additionally, studies showed that Alg@Cur@Se@ZIF-8 dramatically reduced tumour growth compared to free curcumin in 4T1 tumour-bearing mice. More importantly, the histological study confirmed that the developed drug delivery system successfully inhibited lung and liver metastasis while causing negligible toxicity in vital organs. Overall, due to the excellent inhibitory activity on cancerous cell lines and tumour-bearing animals, Alg@Cur@Se@ZIF-8 can be considered promising for breast cancer therapy.

摘要

在这项研究中,使用了一种新型的由海藻酸钠稳定的硒@沸石咪唑骨架核/壳纳米复合材料来提高姜黄素的抗肿瘤活性。所开发的海藻酸钠稳定的载姜黄素硒@沸石咪唑骨架(Alg@Cur@Se@ZIF-8)的平均直径为 159.6nm,多分散指数<0.25。在 pH 5.4 时,纳米载体中姜黄素的释放量比在 pH 7.4 时高 2.69 倍。裸纳米粒子在浓度为 500μg/mL 时的溶血活性约为 12.16%,而用海藻酸钠覆盖其表面后,这一数值降低至 5.2%。通过研究细胞活力,发现 Alg@Cur@Se@ZIF-8 比纯姜黄素导致更多的细胞死亡。此外,研究表明,与游离姜黄素相比,Alg@Cur@Se@ZIF-8 在 4T1 荷瘤小鼠中显著降低了肿瘤生长。更重要的是,组织学研究证实,所开发的药物输送系统成功抑制了肺癌和肝癌的转移,同时对重要器官的毒性可忽略不计。总的来说,由于对癌细胞系和荷瘤动物具有优异的抑制活性,Alg@Cur@Se@ZIF-8 有望用于乳腺癌的治疗。

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