Gold nanoparticles capped with inclusion complex for the delivery of Chrysin in triple-negative breast cancer.

IF 3.5 4区 医学 Q2 ONCOLOGY
Kamini Velhal, Parvindar Sah, Rajesh Raut, Smitali Patil, Sagar Barage, Jaya Lakkakula, Imran Uddin
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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.

在三阴性乳腺癌中,包合物包裹的金纳米颗粒递送Chrysin。
黄菊花素(chrr)是一种天然存在的具有抗癌潜力的黄酮类化合物,但其水溶性较差,限制了其治疗应用。为了解决这一问题,采用冷冻干燥法在不同的摩尔比(1:1,1:2,1:3,1:4)下合成了CHR的β-环糊精包合物(β-CD),其中1:4的包合效率最高(95.23%),并进行了进一步的研究。然后将这些ic功能化到金纳米颗粒(AuNPs)上,形成CHR-β-CD-AuNPs,增强药物传递和稳定性。通过紫外可见光谱(UV-Vis)、红外光谱(FTIR)、核磁共振(NMR)、能谱分析(NTA)和透射电镜(TEM)表征,证实了该材料的包封、氢键和球形形貌,平均粒径约为43 nm。分子对接支持CHR与β-CD之间的强相互作用。体外对人三阴性乳腺癌(MDA-MB-231)细胞的研究表明,CHR-β-CD-AuNPs表现出强大的细胞毒性,IC50为22.17±1.24 mg/L,显著低于CHR/β-CD ICs (IC50: 22.84±1.00 mg/L)和游离CHR (IC50: 100 mg/L, p
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来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
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.
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