植物化学物质及其衍生物是提高癌症患者治疗效率的良好选择。青蒿素（ART）和二甲双胍（MET）广泛应用于治疗各种类型的癌症。然而，由于剂量依赖性副作用和生物利用度差的原因，它们的应用带来了几个挑战。Niosome是一种新型的纳米载体，是封装亲脂性和亲水性药物的最佳选择。本研究合成和表征了PEG基（聚乙二醇）镍脂质体纳米颗粒的不同配方，同时载荷了ART-MET，并评估了它们对A549肺癌细胞的抗癌作用。采用薄膜水合法制备了PEG基Niosome的不同配方并对其大小、形态、释放模式和物理化学结构进行了表征。通过MTT测定评估了自由ART-MET和优化的PEG基镍脂质体纳米颗粒中ART-MET的细胞毒性。此外，采用实时PCR（RT-PCR）技术评估凋亡和抗凋亡基因表达。优化纳米颗粒的尺寸、封装效率（EE）和聚集度指数（PDI）分别为256 nm、95%和0.202。另外，由于PEG化的亲水性特性，考虑到PEG化对降低镍脂质体大小的高影响。根据MTT测定的结果，自由ART-MET和ART-MET负载的镍脂质体纳米颗粒显示剂量依赖性毒性，并抑制A549肺癌细胞的生长。此外，RT-PCR结果表明，ART-MET负载的镍脂质体纳米颗粒通过抑制抗凋亡和诱导凋亡基因在A549肺癌细胞中的表达具有更高的抗增殖作用。我们的研究表明，在优化的PEG基镍脂质体纳米颗粒递送系统中同时使用ART和MET可能是改善肺癌治疗效果的适当方法。©2023年。作者（及）独占许可证Maj Institute of Pharmacology Polish Academy of Sciences。

Phytochemicals and their derivatives are good options to improve treatment efficiency in cancer patients. Artemisinin (ART) and metformin (MET) are widely used phytochemicals to treat various types of cancers. However, their application because of their dose-dependent side effects, and poor bioavailability brings several challenges. Niosome is a novel nanocarrier that is the best choice to encapsulate both lipophilic and hydrophilic drugs. In this study, we synthesized and characterized various formulations of PEGylated (polyethylene glycol) niosomal nanoparticles co-loaded with ART-MET and evaluated their anticancer effect on A549 lung cancer cells.Various formulations of PEGylated noisome were prepared by the thin-film hydration method and characterized in size, morphology, release pattern, and physicochemical structure. The cytotoxic effect of the free ART-MET and optimized PEGylated niosomal nanoparticles loaded with ART-MET on A549 cells were evaluated by MTT assay. Furthermore, the Real-time PCR (RT-PCR) technique used to evaluate apoptotic and anti-apoptotic gene expression.The size, encapsulation efficiency (EE), and polydispersity index (PDI) of the optimized nanoparticles are 256 nm, 95%, and 0.202, respectively. Additionally, due to the PEGylation hydrophilic character, there is a major consideration of the high impact of PEGylation on reducing niosome size. According to the results of the MTT assay, free ART-MET and ART-MET-loaded niosomal nanoparticles showed dose-dependent toxicity and inhibits the growth of A549 lung cancer cells. Furthermore, the RT-PCR results indicated that ART-MET-loaded niosomal nanoparticles have a higher anti-proliferative effect by inhibiting anti-apoptotic and inducing apoptotic gene expression in A549 lung cancer cells.Our study revealed that the simultaneous use of ART and MET in the optimized PEGylated niosomal nanoparticles delivery system could be an appropriate approach to improve the effectiveness of lung cancer treatment.© 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.