背景:黑色素瘤对人类健康构成重大威胁,使开发安全有效的治疗成为一个关键的挑战。双硫仑(DS)是一种经过验证的抗癌药物,当与铜(DS-Cu络合物)组合使用时已显示出有效性。
目的:本研究的重点是将DS-铜配合物封装到聚乙烯醇(PVA)(DS-Cu@PVA)的纳米纤维支架中。为了增加对黑色素瘤细胞系的生物利用度并降低其毒性。
方法:通过使用水溶液的静电纺丝工艺制造支架,随后使用ART-傅里叶变换红外光谱(ART-FTIR)进行分析,扫描电子显微镜(SEM),和能量色散X射线分析(EDX)。此外,细胞毒性,流式细胞术分析,并测定caspase3活性以进一步表征支架。
结果:结果证实,通过不同的表征,将DS-Cu配合物封装到PVA中是成功的。扫描电子显微镜(SEM)分析显示,尽管添加了DS-Cu,纳米纤维的直径仍保持一致。此外,ATR-FTIR证实,将DS-Cu掺入PVA中没有显著改变PVA的特征峰。此外,使用人正常皮肤细胞(HFB4)对DS-Cu@PVA纳米纤维支架的细胞毒性评估表明,与无DS-Cu的对应物相比,其生物相容性优异。值得注意的是,DS-Cu的存在通过增加细胞活性氧来维持其促进细胞凋亡的有效性,促凋亡基因表达,和胱天蛋白酶3活性,同时降低人和小鼠黑色素瘤细胞系(分别为A375和B16F10)中的谷胱甘肽水平和癌基因表达。总的来说,这些发现表明,在PVA纳米纤维中添加DS-Cu可以增强其对黑色素瘤细胞的生物相容性和细胞毒性作用,使它们成为生物医学应用的有希望的候选者。
结论:研究结果表明,将DS-Cu靶向递送到PVA纳米纤维支架上是增强DS-Cu对抗黑色素瘤功效的潜在方法。
BACKGROUND: Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex).
OBJECTIVE: This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity.
METHODS: The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold.
RESULTS: The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications.
CONCLUSIONS: The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.