Department of Chemical & Biomolecular Engineering , Sogang University , Seoul 04107 , Korea.
Department of Chemistry and Chemical Biology, Rutgers , The State University of New Jersey , Piscataway , New Jersey 08854 , United States.
ACS Appl Mater Interfaces. 2018 Mar 21;10(11):9301-9309. doi: 10.1021/acsami.7b19255. Epub 2018 Mar 12.
In the present study, we fabricated magnetic oleosomes functionalized with recombinant proteins as a new carrier for oil-based lipophilic drugs for cancer treatment. The bioengineered oleosome is composed of neutral lipids surrounded by a phospholipid monolayer with embedded oleosin fusion proteins. The oleosin was genetically fused to a nanobody of a green fluorescent protein (GFP). A recombinant protein consisting of immunoglobulin-binding protein LG fused to GFP was used to couple the oleosome to an antibody for targeted delivery to breast cancer cells. The lipid core of the oleosome was loaded with magnetic nanoparticles and carmustine as the lipophilic drug. The magnetic oleosome was characterized using transmission electron microscopy and dynamic light scattering. Moreover, the specific delivery of oleosome into the target cancer cell was investigated via confocal microscopy. To examine the cell viability of the delivered oleosome, a conventional 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was carried out. Furthermore, an animal study was conducted to confirm the effect resulting from the delivery of the anticancer drug-loaded oleosomes. Taken together, the fabricated lipophilic drug-loaded magnetic oleosome can be a powerful tool for oil-based drug delivery agent for cancer therapy.
在本研究中,我们制备了磁性油体,其表面功能化有重组蛋白,用作治疗癌症的新型油溶性亲脂性药物载体。该生物工程油体由中性脂质组成,周围是由嵌入的油质蛋白融合蛋白的磷脂单层包围。油质蛋白通过基因融合到绿色荧光蛋白(GFP)的纳米抗体上。由免疫球蛋白结合蛋白 LG 融合到 GFP 组成的重组蛋白被用来将油体与抗体偶联,以实现对乳腺癌细胞的靶向递送。油体的脂质核心被装载了磁性纳米颗粒和卡莫司汀作为亲脂性药物。通过透射电子显微镜和动态光散射对磁性油体进行了表征。此外,通过共聚焦显微镜研究了油体向目标癌细胞的特异性递送。为了检查递送的油体的细胞活力,进行了常规的 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定。此外,还进行了动物研究以确认载有抗癌药物的油体递送的效果。总之,所制备的载有亲脂性药物的磁性油体可以成为癌症治疗用油基药物递送剂的有力工具。