Synthesis of 5-Fluorouracil (5-FU) coated platinum nanoparticles and apoptotic effects on U87 human glioblastoma cells.

IF 6 2区 医学 Q1 ONCOLOGY
Atena Abed, Merat Karimi, Majid Nejati, Michael R Hamblin, Seyed Abbas Mirzaei, Mostafa Sarvizadeh, Hamed Mirzaei
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引用次数: 0

Abstract

Background: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent; however, its clinical application is often limited by systemic toxicity and the development of drug resistance. To enhance its therapeutic efficacy, novel drug delivery strategies are under investigation. This study evaluated the use of platinum nanoparticles (PtNPs) as a nanocarrier system for 5-FU delivery to glioblastoma cells, focusing on their effects on apoptosis-related proteins.

Methods: The binding affinity and interactions of 5-FU with key apoptotic proteins (BAX, Bcl2, and Caspase-3) were assessed using molecular docking and validated through molecular dynamics (MD) simulations. PtNPs were synthesized and characterized via scanning electron microscopy (SEM), X-ray diffraction (XRD), and dynamic light scattering (DLS). Drug loading and encapsulation efficiency were determined, and cytotoxicity assays were conducted in U87 glioblastoma cells. The expression levels of apoptosis-related genes and proteins were evaluated to determine the biological impact of the formulations.

Results: Docking results confirmed effective binding of 5-FU to Bcl2, Caspase-3, and BAX, with MD simulations supporting stable complex formation, particularly with Bcl2 and Caspase-3. The synthesized PtNPs exhibited favorable physicochemical properties, including uniform morphology and high drug loading efficiency. In vitro release studies revealed a sustained release profile for the PtNPs/5-FU formulation. Furthermore, PtNPs/5-FU significantly downregulated the expression of EMT- and proliferation-related genes (cyclin D1, ZEB1, and Twist) and suppressed Bcl2 protein levels, resulting in enhanced apoptosis in U87 cells.

Conclusion: PtNPs effectively functioned as a delivery platform for 5-FU, improving its release kinetics and promoting apoptotic responses while potentially minimizing systemic toxicity. These findings support further exploration of PtNP-based drug delivery systems as a promising strategy for glioblastoma treatment.

Abstract Image

Abstract Image

Abstract Image

5-氟尿嘧啶(5-FU)包被铂纳米颗粒的合成及其对人胶质瘤细胞凋亡的影响。
背景:5-氟尿嘧啶(5-FU)是一种广泛使用的化疗药物;然而,它的临床应用往往受到全身毒性和耐药性的限制。为了提高其治疗效果,新的给药策略正在研究中。本研究评估了铂纳米颗粒(PtNPs)作为5-FU递送至胶质母细胞瘤细胞的纳米载体系统的使用,重点关注其对凋亡相关蛋白的影响。方法:采用分子对接方法评估5-FU与关键凋亡蛋白(BAX、Bcl2和Caspase-3)的结合亲和力和相互作用,并通过分子动力学(MD)模拟验证。合成了PtNPs,并通过扫描电镜(SEM)、x射线衍射(XRD)和动态光散射(DLS)进行了表征。测定了U87胶质母细胞瘤细胞的载药量和包封效率,并进行了细胞毒性试验。评估细胞凋亡相关基因和蛋白的表达水平,以确定制剂的生物学影响。结果:对接结果证实了5-FU与Bcl2、Caspase-3和BAX的有效结合,MD模拟支持稳定的复合物形成,特别是与Bcl2和Caspase-3。合成的PtNPs具有良好的物理化学性质,具有均匀的形态和较高的载药效率。体外释放研究显示PtNPs/5-FU制剂具有缓释特性。此外,PtNPs/5-FU显著下调EMT和增殖相关基因(cyclin D1、ZEB1和Twist)的表达,抑制Bcl2蛋白水平,导致U87细胞凋亡增强。结论:PtNPs有效地作为5-FU的递送平台,改善其释放动力学,促进凋亡反应,同时潜在地减少全身毒性。这些发现支持进一步探索基于ptnp的药物输送系统作为胶质母细胞瘤治疗的有希望的策略。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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