山奈酚和索拉非尼与聚乙二醇化金纳米颗粒联合递送乳腺癌:细胞毒性和诱导凋亡的研究

Yunxin Zhang, Jiange Liu
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摘要

目前临床治疗浸润性乳腺癌的方法疗效低,全身不良反应大,患者依从性差。在这项研究中,我们开发了双抗癌药物(索拉非尼(SFB)和山奈酚(KMF))封装在聚乙二醇化金纳米材料(PEG-AuNPs@SFB/KMF)中,用于针对乳腺癌的药物输送系统,以避免这一问题。随后的研究考察了pH值是否影响药物释放。目前的研究结果表明,索拉非尼和山奈酚联合使用比单独使用更能引起细胞毒性作用。体外细胞毒性研究证实PEG-AuNPs@SFB/KMF在MCF-7和MDA-MB-231细胞中比单独使用索拉非尼更有效,对NIH3T3细胞的毒性更小。通过Click-iT EdU实验检测癌细胞增殖,表明NPs能有效诱导癌细胞凋亡。不同的生化染色方法(吖啶橙和溴化乙啶(AO-EB)和核染色(DAPI))证实了细胞的形态学调查。PEG-AuNPs@SFB/KMF增加细胞凋亡率,Annexin V-FITC/PI染色流式细胞分析证实。因此,我们相信构建的基于纳米颗粒递送的多功能纳米载体可能是乳腺癌治疗的替代治疗策略。图形抽象
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Facile fabrication of combination delivery of kaempferol and sorafenib with PEGylated gold nanoparticles delivery to breast cancer: Investigation of cytotoxicity and apoptosis induction
Abstract Current clinical therapies for invasive breast cancer have low therapeutic effectiveness and substantial systemic adverse effects, leading to poor patient compliance. In this investigation, we developed dual anticancer drugs (sorafenib (SFB) and kaempferol (KMF)) encapsulated in PEGylated gold nanomaterial (PEG-AuNPs@SFB/KMF) for a drug delivery system targeting breast cancer to circumvent this problem. Subsequent research examined whether pH affects drug release. The current study results show that sorafenib and kaempferol work better together than each treatment individually in eliciting cytotoxic effects. In vitro cytotoxicity studies confirmed that PEG-AuNPs@SFB/KMF were more effective than sorafenib alone in MCF-7 and MDA-MB-231 cells, with less toxicity in NIH3T3 cells. The cancer cell proliferation was measured by Click-iT EdU assay, which indicates that the NPs effectively induce apoptosis in cancer cells. The different biochemical staining (acridine orange and ethidium bromide (AO-EB and nuclear staining (DAPI)) methods confirmed the morphological investigation of the cells. PEG-AuNPs@SFB/KMF increased apoptosis ratio, confirmed by flow cytometric analysis via Annexin V-FITC/PI staining methods. Therefore, we believe that the built multifunctional nanocarrier based on developed nanoparticle delivery could be an alternative therapeutic strategy for breast cancer therapy. Graphical Abstract
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