Biochemistry Department, Faculty of Science, Ege University, Bornova, Izmir, 35100, Turkey.
Biochemistry Department, Faculty of Science, Ege University, Bornova, Izmir, 35100, Turkey.
Arch Biochem Biophys. 2020 Nov 30;695:108643. doi: 10.1016/j.abb.2020.108643. Epub 2020 Oct 22.
Artificial nanostructures using polymers to produce polymeric vesicles are inspired by the many intricate structures found in living organisms. Polymersomes are a class of self-assembled vesicles known for their great stability and application in drug delivery. They can be tuned according to their intended use by changing their components and introducing activable block copolymers that transform these polymersomes into smart nanocarriers. In this study, we propose the synthesis of a poly (ethylene oxide)-poly (ε-caprolactone)-based polymersome (PEO-PCL) loaded with GSH as a pH-responsive drug delivery molecule for cancer and protein alteration inhibition. Initially, the nanocarrier was synthesized and characterized by DLS, TEM/SEM microscopy as well as gel permeation chromatography (GPC) and H NMR. Their CMC formation, encapsulation efficiency, and pH responsiveness were analyzed. In addition, empty and GSH-loaded PEO-PCL polymersomes were tested for their toxicity and therapeutic effect on normal and cancer cells via an MTT test. Subsequently, protein alteration models (aggregation, glycation, and oxidation) were performed in vitro where the polymersomes were tested. Results showed that other than being non-toxic and able to highly encapsulate and release the GSH in response to acidic conditions, the nanocomposites do not hinder its content's ameliorative effects on cancer cells and protein alterations. This infers that polymeric nanocarriers can be a base for future smart biomedicine applications and theranostics.
利用聚合物人工构建纳米结构来产生聚合物囊泡,这一灵感源自于在生物体中发现的许多复杂结构。聚合物囊泡是一类自组装囊泡,因其具有极好的稳定性而被广泛应用于药物传递。通过改变其组成成分,并引入可激活的嵌段共聚物,可以将聚合物囊泡调制成智能纳米载体。在本研究中,我们提出了一种基于聚(氧化乙烯)-聚(ε-己内酯)的聚合物囊泡(PEO-PCL)的合成方法,该囊泡负载谷胱甘肽(GSH)作为一种 pH 响应性药物输送分子,用于癌症和蛋白质改变抑制。首先,通过动态光散射(DLS)、透射电子显微镜/扫描电子显微镜(TEM/SEM)、凝胶渗透色谱(GPC)和核磁共振(NMR)对纳米载体进行了合成和表征。分析了它们的临界胶束浓度(CMC)形成、包封效率和 pH 响应性。此外,通过 MTT 试验测试了空的和负载 GSH 的 PEO-PCL 聚合物囊泡对正常和癌细胞的毒性和治疗效果。随后,在体外进行了蛋白质改变模型(聚集、糖化和氧化)实验,对聚合物囊泡进行了测试。结果表明,除了具有非毒性、能够高度包封并响应酸性条件释放 GSH 之外,纳米复合材料不会阻碍其对癌细胞和蛋白质改变的改善作用。这推断出聚合物纳米载体可以成为未来智能生物医学应用和治疗学的基础。