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静电纺丝法制备含双硫仑-铜配合物的聚乙烯醇纳米纤维:一种潜在的抗黑色素瘤给药系统。

Preparation of poly(vinyl alcohol) nanofibers containing disulfiram-copper complex by electrospinning: a potential delivery system against melanoma.

机构信息

Polymer Materials Research Department, Advanced Technology and New Materials Research Institute, City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab City, 21934, Alexandria, Egypt.

Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab City, 21934, Alexandria, Egypt.

出版信息

Daru. 2024 Dec;32(2):573-583. doi: 10.1007/s40199-024-00527-w. Epub 2024 Jul 4.

Abstract

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).

OBJECTIVES

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.

CONCLUSION

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.

摘要

背景

黑色素瘤对人类健康构成重大威胁,因此开发安全有效的治疗方法是一项重大挑战。双硫仑(DS)是一种经过验证的抗癌药物,与铜(DS-Cu 配合物)联合使用时已显示出疗效。

目的

本研究专注于将 DS-铜配合物封装到由聚乙烯醇(PVA)制成的纳米纤维支架中(DS-Cu@PVA)。为了提高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备支架,并使用 ART-傅里叶变换红外光谱(ART-FTIR)、扫描电子显微镜(SEM)和能量色散 X 射线分析(EDX)对其进行分析。此外,还进行了细胞毒性、流式细胞术分析和 caspase 3 活性测定,以进一步表征支架。

结果

结果证实,通过不同的表征成功地将 DS-Cu 配合物封装到 PVA 中。扫描电子显微镜(SEM)分析表明,尽管添加了 DS-Cu,但纳米纤维的直径仍保持不变。此外,ATR-FTIR 证实,DS-Cu 掺入 PVA 并未显著改变 PVA 的特征峰。此外,使用人正常皮肤细胞(HFB4)对 DS-Cu@PVA 纳米纤维支架进行的细胞毒性评估表明,与不含 DS-Cu 的支架相比,它具有更好的生物相容性。值得注意的是,DS-Cu 的存在通过增加细胞活性氧物质、促凋亡基因表达和 caspase 3 活性,同时降低人黑色素瘤细胞系(A375)和小鼠黑色素瘤细胞系(B16F10)中的谷胱甘肽水平和致癌基因表达,保持了其促进细胞凋亡的功效。总之,这些发现表明,将 DS-Cu 添加到 PVA 纳米纤维中可增强其对黑色素瘤细胞的生物相容性和细胞毒性作用,使其成为生物医学应用的有前途的候选物。

结论

研究结果表明,将 DS-Cu 靶向递送到 PVA 纳米纤维支架上可能是提高 DS-Cu 治疗黑色素瘤疗效的一种方法。

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