{"title":"Cisplatin-loaded UiO-66-NH<sub>2</sub> functionalized with folic acid enhances apoptotic activity and antiproliferative effects in MDA-MB-231 breast and A2780 ovarian cancer cells: An <i>in vitro</i> study.","authors":"Zahra Sadeghi Jam, Farzaneh Tafvizi, Parvin Khodarahmi, Parvaneh Jafari, Fahimeh Baghbani-Arani","doi":"10.1016/j.heliyon.2025.e42685","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>BAX</i> and <i>P53</i> gene expression, alongside the downregulation of <i>BCL2, CCND1,</i> and <i>CDK4.</i> 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.</p>","PeriodicalId":12894,"journal":{"name":"Heliyon","volume":"11 4","pages":"e42685"},"PeriodicalIF":3.4000,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904574/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heliyon","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.heliyon.2025.e42685","RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/28 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Cisplatin-loaded UiO-66-NH2 functionalized with folic acid enhances apoptotic activity and antiproliferative effects in MDA-MB-231 breast and A2780 ovarian cancer cells: An in vitro study.
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 BAX and P53 gene expression, alongside the downregulation of BCL2, CCND1, and CDK4. 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.
期刊介绍:
Heliyon is an all-science, open access journal that is part of the Cell Press family. Any paper reporting scientifically accurate and valuable research, which adheres to accepted ethical and scientific publishing standards, will be considered for publication. Our growing team of dedicated section editors, along with our in-house team, handle your paper and manage the publication process end-to-end, giving your research the editorial support it deserves.