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负载顺铂的叶酸功能化UiO-66-NH增强MDA-MB-231乳腺癌细胞和A2780卵巢癌细胞的凋亡活性和抗增殖作用:一项研究。

Cisplatin-loaded UiO-66-NH functionalized with folic acid enhances apoptotic activity and antiproliferative effects in MDA-MB-231 breast and A2780 ovarian cancer cells: An study.

作者信息

Sadeghi Jam Zahra, Tafvizi Farzaneh, Khodarahmi Parvin, Jafari Parvaneh, Baghbani-Arani Fahimeh

机构信息

Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran.

Microbiology Department, Faculty of Science, Arak Branch, Islamic Azad University, Arak, Iran.

出版信息

Heliyon. 2025 Feb 14;11(4):e42685. doi: 10.1016/j.heliyon.2025.e42685. eCollection 2025 Feb 28.

Abstract

The multifunctional nature of UiO-66-NH₂ as a drug carrier positions it as an optimal candidate for encapsulating and delivering anticancer agents. This study developed a folic acid (FA)-functionalized metal-organic framework (MOF) based on UiO-66-NH₂ to facilitate the targeted delivery of cisplatin (CIS) to MDA-MB-231 breast cancer and A2780 ovarian cancer cells. Fourier transform infrared spectroscopy (FT-IR) confirmed the successful encapsulation of CIS within UiO-66-NH₂, while the drug release profile demonstrated a sustained, pH-responsive release of CIS, with a pronounced increase in the acidic tumor microenvironment. The MTT assay revealed excellent biocompatibility of UiO-66-NH₂-FA with HFF healthy cells, whereas UiO-66-NH₂-CIS-FA significantly enhanced anticancer activity against MDA-MB-231 and A2780 cells. Treatment with UiO-66-NH₂-CIS-FA induced substantial apoptosis in both cell lines, leading to a marked upregulation of and gene expression, alongside the downregulation of and Furthermore, cells treated with CIS, UiO-66-NH₂-CIS, and UiO-66-NH₂-CIS-FA exhibited a significant increase in DCF fluorescence compared to the control group, indicating elevated ROS generation. UiO-66-NH₂-CIS-FA demonstrated enhanced drug-loading capacity and cytotoxic efficacy against cancer cells. Functionalization of UiO-66-NH₂-CIS with FA presents a promising strategy for targeted cancer therapy by improving drug delivery specificity and enhancing therapeutic outcomes.

摘要

UiO-66-NH₂作为药物载体的多功能性质使其成为封装和递送抗癌药物的理想候选者。本研究基于UiO-66-NH₂开发了一种叶酸(FA)功能化的金属有机框架(MOF),以促进顺铂(CIS)向MDA-MB-231乳腺癌细胞和A2780卵巢癌细胞的靶向递送。傅里叶变换红外光谱(FT-IR)证实CIS成功封装在UiO-66-NH₂中,而药物释放曲线表明CIS具有持续的、pH响应性释放,在酸性肿瘤微环境中释放明显增加。MTT分析显示UiO-66-NH₂-FA与HFF健康细胞具有良好的生物相容性,而UiO-66-NH₂-CIS-FA显著增强了对MDA-MB-231和A2780细胞的抗癌活性。用UiO-66-NH₂-CIS-FA处理诱导了两种细胞系中的大量凋亡,导致 和 基因表达明显上调,同时 和 下调。此外,与对照组相比,用CIS、UiO-66-NH₂-CIS和UiO-66-NH₂-CIS-FA处理的细胞显示DCF荧光显著增加,表明活性氧生成增加。UiO-66-NH₂-CIS-FA显示出增强的载药能力和对癌细胞的细胞毒性功效。用FA对UiO-66-NH₂-CIS进行功能化通过提高药物递送特异性和增强治疗效果,为靶向癌症治疗提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ffc/11904574/350334d5894d/ga1.jpg

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