{"title":"Curcumin and doxorubicin encapsulated in biocompatible clay-based nanomaterial: A strategy to overcome multidrug resistance","authors":"Paola Poma, Marina Massaro, Salvatrice Rigogliuso, Lucia Condorelli, Rita Sánchez-Espejo, César Viseras, Monica Notarbartolo, Serena Riela","doi":"10.1002/ardp.202400702","DOIUrl":null,"url":null,"abstract":"<p>Multidrug resistance (MDR) due to the overexpression of the P-glycoprotein (P-gp) efflux pump remains a significant challenge in cancer therapy, also in breast cancer. Traditional pharmacological approaches have focused on using inhibitors to modulate P-gp expression and function. Curcumin, a polyphenol derived from <i>Curcuma longa</i> L., is one of the most extensively studied natural compounds with the potential as an effective P-gp inhibitor. Despite its promising attributes, the clinical application of P-gp inhibitors is complicated by P-gp's presence in healthy cells, such as those in the intestinal barrier and blood–brain barrier, which can lead to increased toxicity. To address these challenges, we developed a novel multifunctional nanomaterial by covalently bonding halloysite nanotubes (HNTs) with hectorite (Ht) and loading it with curcumin and doxorubicin. The efficacy of the co-delivery of curcumin and doxorubicin by HNTs-Ht nanomaterial was evaluated by cytotoxicity assays on MCF-7R cells, both in two-dimensional (2D) and in three-dimensional (3D) models. The obtained data show that curcumin causes increased doxorubicin accumulation by acting as a substrate for P-gp transport and as a stimulator of the adenosine triphosphate (ATP)-dependent drug efflux transporter on a doxorubicin-resistant breast cancer cell line. The results suggest that the HNTs-Ht nanomaterial could provide a promising approach to improve chemotherapy effectiveness by overcoming MDR and enhancing treatment outcomes.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671670/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archiv der Pharmazie","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ardp.202400702","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Multidrug resistance (MDR) due to the overexpression of the P-glycoprotein (P-gp) efflux pump remains a significant challenge in cancer therapy, also in breast cancer. Traditional pharmacological approaches have focused on using inhibitors to modulate P-gp expression and function. Curcumin, a polyphenol derived from Curcuma longa L., is one of the most extensively studied natural compounds with the potential as an effective P-gp inhibitor. Despite its promising attributes, the clinical application of P-gp inhibitors is complicated by P-gp's presence in healthy cells, such as those in the intestinal barrier and blood–brain barrier, which can lead to increased toxicity. To address these challenges, we developed a novel multifunctional nanomaterial by covalently bonding halloysite nanotubes (HNTs) with hectorite (Ht) and loading it with curcumin and doxorubicin. The efficacy of the co-delivery of curcumin and doxorubicin by HNTs-Ht nanomaterial was evaluated by cytotoxicity assays on MCF-7R cells, both in two-dimensional (2D) and in three-dimensional (3D) models. The obtained data show that curcumin causes increased doxorubicin accumulation by acting as a substrate for P-gp transport and as a stimulator of the adenosine triphosphate (ATP)-dependent drug efflux transporter on a doxorubicin-resistant breast cancer cell line. The results suggest that the HNTs-Ht nanomaterial could provide a promising approach to improve chemotherapy effectiveness by overcoming MDR and enhancing treatment outcomes.
由于p -糖蛋白(P-gp)外排泵的过度表达引起的多药耐药(MDR)仍然是癌症治疗中的一个重大挑战,包括乳腺癌。传统的药理学方法集中在使用抑制剂来调节P-gp的表达和功能。姜黄素(Curcuma longa L.)是一种从姜黄中提取的多酚,是研究最广泛的天然化合物之一,具有有效的P-gp抑制剂的潜力。尽管P-gp抑制剂具有很好的特性,但由于P-gp存在于健康细胞(如肠屏障和血脑屏障)中,可能导致毒性增加,因此P-gp抑制剂的临床应用变得复杂。为了解决这些问题,我们开发了一种新的多功能纳米材料,通过将高岭土纳米管(HNTs)与赫克托石(Ht)共价结合,并在其上装载姜黄素和阿霉素。通过对MCF-7R细胞进行二维(2D)和三维(3D)模型的细胞毒性试验,评估了HNTs-Ht纳米材料共同递送姜黄素和阿霉素的效果。获得的数据表明,姜黄素通过作为P-gp运输的底物和作为三磷酸腺苷(ATP)依赖性药物外排转运体的刺激剂,在阿霉素耐药的乳腺癌细胞系上引起阿霉素积累增加。结果表明,HNTs-Ht纳米材料可以通过克服耐多药耐药和提高治疗效果来提高化疗效果。
期刊介绍:
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.