{"title":"Gold nanoparticles capped with inclusion complex for the delivery of Chrysin in triple-negative breast cancer.","authors":"Kamini Velhal, Parvindar Sah, Rajesh Raut, Smitali Patil, Sagar Barage, Jaya Lakkakula, Imran Uddin","doi":"10.1007/s12032-025-03011-w","DOIUrl":null,"url":null,"abstract":"<p><p>Chrysin (CHR), a naturally occurring flavonoid with promising anticancer potential, suffers from poor water solubility, limiting its therapeutic applications. To address this, β-Cyclodextrin (β-CD) inclusion complexes (ICs) of CHR were synthesized via the freeze-drying method at varying molar ratios (1:1, 1:2, 1:3, 1:4), with the 1:4 ratio exhibiting the highest entrapment efficiency (95.23%) and selected for further study. These ICs were then functionalized onto gold nanoparticles (AuNPs) to develop CHR-β-CD-AuNPs, enhancing drug delivery and stability. Characterization by UV-Vis, FTIR, NMR, NTA, and TEM confirmed successful encapsulation, hydrogen bonding, and spherical morphology with an average particle size of ~ 43 nm. Molecular docking supported strong interactions between CHR and β-CD. In vitro studies against human triple-negative breast cancer (MDA-MB-231) cells demonstrated that CHR-β-CD-AuNPs exhibited potent cytotoxicity with an IC<sub>50</sub> of 22.17 ± 1.24 mg/L, significantly lower than CHR/β-CD ICs (IC<sub>50</sub>: 22.84 ± 1.00 mg/L) and free CHR (IC<sub>50</sub> > 100 mg/L, p < 0.001). Hoechst and phalloidin staining revealed clear apoptotic features such as nuclear fragmentation and cytoskeletal disruption. Gene expression analysis showed upregulation of Bax and Caspase-3 and downregulation of Bcl-2, confirming apoptosis induction. Furthermore, scratch wound assays demonstrated significant inhibition of cancer cell migration, with wound closure reduced to 8.38 ± 0.74% (IC) and 15.27 ± 1.05% (IC-AuNPs) compared to 74.41 ± 1.22% in untreated controls (p < 0.001). These findings establish that β-CD-based CHR-AuNP nanocarriers substantially improve the solubility, stability, and therapeutic efficacy of CHR, offering a promising nanoformulations strategy for enhanced targeted breast cancer therapy.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"441"},"PeriodicalIF":3.5000,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12032-025-03011-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Chrysin (CHR), a naturally occurring flavonoid with promising anticancer potential, suffers from poor water solubility, limiting its therapeutic applications. To address this, β-Cyclodextrin (β-CD) inclusion complexes (ICs) of CHR were synthesized via the freeze-drying method at varying molar ratios (1:1, 1:2, 1:3, 1:4), with the 1:4 ratio exhibiting the highest entrapment efficiency (95.23%) and selected for further study. These ICs were then functionalized onto gold nanoparticles (AuNPs) to develop CHR-β-CD-AuNPs, enhancing drug delivery and stability. Characterization by UV-Vis, FTIR, NMR, NTA, and TEM confirmed successful encapsulation, hydrogen bonding, and spherical morphology with an average particle size of ~ 43 nm. Molecular docking supported strong interactions between CHR and β-CD. In vitro studies against human triple-negative breast cancer (MDA-MB-231) cells demonstrated that CHR-β-CD-AuNPs exhibited potent cytotoxicity with an IC50 of 22.17 ± 1.24 mg/L, significantly lower than CHR/β-CD ICs (IC50: 22.84 ± 1.00 mg/L) and free CHR (IC50 > 100 mg/L, p < 0.001). Hoechst and phalloidin staining revealed clear apoptotic features such as nuclear fragmentation and cytoskeletal disruption. Gene expression analysis showed upregulation of Bax and Caspase-3 and downregulation of Bcl-2, confirming apoptosis induction. Furthermore, scratch wound assays demonstrated significant inhibition of cancer cell migration, with wound closure reduced to 8.38 ± 0.74% (IC) and 15.27 ± 1.05% (IC-AuNPs) compared to 74.41 ± 1.22% in untreated controls (p < 0.001). These findings establish that β-CD-based CHR-AuNP nanocarriers substantially improve the solubility, stability, and therapeutic efficacy of CHR, offering a promising nanoformulations strategy for enhanced targeted breast cancer therapy.
期刊介绍:
Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.