Efficient Delivery of Gold Nanoparticles and miRNA-33a Via Cationic PEGylated Niosomal Formulation to MCF-7 Breast Cancer Cells

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-09-12 DOI:10.1208/s12249-024-02906-7

Seyedeh Melika Ahmadi, Mohammad Seyedabadi, Pedram Ebrahimnejad, Mozhgan Abasi, Ali Nokhodchi

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Abstract

To overcome the challenges associated with the co-delivery of AuNPs (gold nanoparticles) and miRNA as an anti-breast cancer combination therapy, niosomal systems were developed using Span 60, cholesterol, and a cationic lipid (CTAB), and the formulations were optimized using Box-Behnken experimental design. The niosomal formulations with the smallest size were selected for further optimization of size, surface charge, entrapment efficiency, and stability. To achieve this, AuNPs and DSPE-PEG2000 (2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000)were added to the formulation. The optimized niosomal formulation could effectively encapsulate AuNPs with an entrapment efficiency of 34.49% ± 0.84 and a spherical particle size of 153.6 ± 4.62 nm. The incorporation of PEG and CTAB led to notable enhancements in the overall characteristics of the delivery system. To evaluate the effectiveness of the combination therapy, various assessments such as cytotoxicity, apoptosis, and gene expression properties were conducted. The results demonstrated that the combination delivery using the new C-PEG-Nio-AuNPs (cationic pegylated niosomal gold nanoparticles) system and miRNA had the lowest IC50, the highest apoptosis rate, and the most significant upregulation of miRNA and BAX/BCL2 expression in MCF-7 cell growth. In conclusion, this innovative co-delivery approach represents a promising breakthrough in the development of therapeutic agents for breast cancer treatment. By combining multiple therapeutic agents within a single delivery system, this method has the potential to enhance treatment efficacy, reduce side effects, and improve patient outcomes.

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通过阳离子 PEG 化 Niosomal 配方向 MCF-7 乳腺癌细胞高效递送金纳米粒子和 miRNA-33a

为了克服将 AuNPs（金纳米粒子）和 miRNA 共同递送作为抗乳腺癌联合疗法所面临的挑战，研究人员使用 Span 60、胆固醇和阳离子脂质（CTAB）开发了纳米体系统，并使用 Box-Behnken 实验设计对配方进行了优化。筛选出尺寸最小的纳米口服液配方，进一步优化其尺寸、表面电荷、包载效率和稳定性。为此，在配方中添加了 AuNPs 和 DSPE-PEG2000（2-二硬脂酰-sn-甘油-3-磷乙醇胺-N-[氨基（聚乙二醇）-2000）。优化后的niosomal制剂能有效地包封AuNPs，包封效率为34.49% ± 0.84，球形粒径为153.6 ± 4.62 nm。PEG 和 CTAB 的加入显著提高了给药系统的整体特性。为了评估组合疗法的有效性，研究人员进行了细胞毒性、细胞凋亡和基因表达特性等多项评估。结果表明，使用新型 C-PEG-Nio-AuNPs（阳离子聚合纳米金颗粒）系统和 miRNA 的联合给药具有最低的 IC50 值、最高的凋亡率，以及对 MCF-7 细胞生长中 miRNA 和 BAX/BCL2 表达最显著的上调作用。总之，这种创新的联合给药方法是乳腺癌治疗药物开发领域的一个有希望的突破。通过在单一给药系统中结合多种治疗剂，这种方法有望提高疗效、减少副作用并改善患者预后。

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