Department of Materials Science & Engineering, Iowa State University, Ames, IA 50011, United States.
Department of Materials Science & Engineering, Iowa State University, Ames, IA 50011, United States; Department of Chemical & Biological Engineering, Iowa State University, Ames, IA 50011, United States; Division of Materials Science & Engineering, Ames National Laboratory, Ames, IA 50011, United States.
Mater Sci Eng C Mater Biol Appl. 2017 Oct 1;79:237-244. doi: 10.1016/j.msec.2017.05.032. Epub 2017 May 10.
Liposomes are one of the most widely studied drug carriers due to their relative biocompatibility, lack of immune system stimulation, ability to be cell specific, and serve as a protective drug carrier. Due to several physicochemical properties such as size and charge, liposomes naturally target the phagocytic capabilities of macrophages. In the tumor microenvironment, macrophages strongly influence growth and progression, making them an appealing target for drug delivery. Using the natural capability of liposomes to target macrophages, and the knowledge that material properties can alter cellular responses, this work aims to influence macrophage phenotype with arginine-like surface modified DOPE:DOPC liposomes. These liposomes were incubated with interleukin-4 (IL-4) or lipopolysaccharide (LPS) stimulated macrophages and naïve RAW 264.7 macrophages. Macrophage phenotype was determined through arginase activity, tumor necrosis factor (TNF)-α secretion, and nitrite production. With significant variations in the molecular profiles of each activated cell type, these findings suggest that macrophage responses could be altered with small variations in surface functionality of liposomes.
脂质体由于其相对的生物相容性、缺乏免疫系统刺激、能够具有细胞特异性以及作为保护性药物载体而成为最广泛研究的药物载体之一。由于大小和电荷等多种物理化学性质,脂质体自然靶向巨噬细胞的吞噬能力。在肿瘤微环境中,巨噬细胞强烈影响肿瘤的生长和进展,使其成为药物递送的有吸引力的靶标。利用脂质体靶向巨噬细胞的天然能力,以及材料性质可以改变细胞反应的知识,这项工作旨在通过具有精氨酸样表面修饰的 DOPE:DOPC 脂质体影响巨噬细胞表型。将这些脂质体与白细胞介素 4 (IL-4) 或脂多糖 (LPS) 刺激的巨噬细胞和幼稚 RAW 264.7 巨噬细胞一起孵育。通过精氨酸酶活性、肿瘤坏死因子 (TNF)-α 分泌和亚硝酸盐产生来确定巨噬细胞表型。由于每种激活细胞类型的分子谱存在显著差异,这些发现表明,通过脂质体表面功能的微小变化可以改变巨噬细胞的反应。