Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran.
Sci Rep. 2024 Nov 9;14(1):27380. doi: 10.1038/s41598-024-78817-1.
Two strategies were employed to modify the performance of the nano-niosome drug delivery system. Initially, the surface of the nano-niosomes underwent modification through the inclusion of polyethylene glycol, thereby altering its properties. Additionally, the core of the nano-niosomes was equipped with FeO magnetic nanoparticles to impart magnetic characteristics to the system. This study presents the development of PEGylated magnetic nanoniosomes (PMNios) for the co-delivery of artemisinin (ART) and metformin (MET) in cancer therapy, highlighting significant advancements in chemotherapeutic efficacy. The magnetization of the nano-niosomes facilitated the targeted delivery of drugs to specific tissues, while PEGylation improved the bioavailability of the nano-niosomes. These PEGylated magnetic niosomes (PMNios) were then loaded with artemisinin and metformin drugs. The synthesized PMNios were thoroughly evaluated in terms of zeta potential, size, morphology, and entrapment efficiency. The PMNios achieved a drug loading efficiency of 88%. They exhibited an average size of 298 nm, a polydispersity index of 0.32, and a zeta potential of - 19 mV, indicating the complete stability. SEM and TEM images of the PMNios revealed a spherical morphology. Subsequently, the PMNios were compared with other forms of nano-niosomes, including empty niosomes, non-magnetic niosomes, and non-PEGylated niosomes. The encapsulation of the nano-niosomes with magnetic nanoparticles allows for faster delivery of the encapsulated drugs to the tumor site, while PEGylation improved the stability, bioavailability, and controlled release of the PMNios. Furthermore, the in-vitro effectiveness of various formulations of the PMNios against A549, a lung cancer cell line, demonstrated that the PMNios exhibited appropriate toxicity towards cancer cell lines in the presence of an external magnetic field. Gene expression level of Bcl2 were lower for the PMNios-ART-MET system, whereas the level of Bax were higher than the other group. The PMNios-ART-MET system also demonstrated well internalization into the A549 cells and preponderant endocytosis. These findings underscore the novelty and potential of PMNios as a robust platform for the targeted co-delivery of hydrophilic and hydrophobic drugs, promising a new frontier in cancer therapy by enhancing the therapeutic index and minimizing side effects.
两种策略被用来改善纳米囊泡药物传递系统的性能。首先,纳米囊泡的表面通过包含聚乙二醇进行修饰,从而改变其性质。此外,纳米囊泡的核心装备有 FeO 磁性纳米粒子,赋予系统磁性。本研究提出了载有青蒿素(ART)和二甲双胍(MET)的聚乙二醇化磁性纳米囊泡(PMNios)用于癌症治疗的联合递药,突出了化疗疗效的显著进展。纳米囊泡的磁化促进了药物靶向递送到特定组织,而 PEG 化提高了纳米囊泡的生物利用度。然后将这些聚乙二醇化磁性纳米囊泡(PMNios)负载青蒿素和二甲双胍药物。合成的 PMNios 在zeta 电位、粒径、形态和包封效率方面进行了全面评估。PMNios 的药物载药效率达到 88%。它们的平均粒径为 298nm,多分散指数为 0.32,zeta 电位为-19mV,表明完全稳定。PMNios 的 SEM 和 TEM 图像显示出球形形态。随后,将 PMNios 与其他形式的纳米囊泡进行比较,包括空纳米囊泡、非磁性纳米囊泡和非 PEG 化纳米囊泡。磁性纳米粒子包封纳米囊泡可实现包裹药物更快地递送到肿瘤部位,而 PEG 化提高了 PMNios 的稳定性、生物利用度和控释性。此外,PMNios 对肺癌细胞系 A549 的各种制剂的体外效果表明,在存在外部磁场的情况下,PMNios 对癌细胞系具有适当的毒性。PMNios-ART-MET 系统的 Bcl2 基因表达水平较低,而 Bax 水平高于其他组。PMNios-ART-MET 系统也表现出良好的内化进入 A549 细胞和优势内吞作用。这些发现突出了 PMNios 作为一种强大的亲水性和疏水性药物联合递药平台的新颖性和潜力,通过提高治疗指数和最小化副作用,为癌症治疗开辟了新的前沿。