Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
J Pharm Sci. 2019 Nov;108(11):3592-3598. doi: 10.1016/j.xphs.2019.07.002. Epub 2019 Jul 6.
Nanosize plasma proteins could be used as a biomimetic drug delivery system (DDS) for cancer treatment when loaded with anticancer drugs based on the fact that plasma proteins can serve as a source of nutrients for cancer cells. This prompted us to investigate the potential of α-acid glycoprotein (AGP) for this role because it is a nanosize plasma protein and binds a variety of anticancer agents. Pharmacokinetic analyses indicated that AGP is distributed more extensively in tumor tissue than human serum albumin, which was already established as a cancer DDS carrier. AGP is possibly being incorporated into tumor cells via endocytosis pathways. Moreover, a synthetic AGP-derived peptide which possesses a high ability to form an α-helix, as deduced from the primary structure of AGP, was also taken up by the tumor cells. AGP loaded with anticancer agents, such as paclitaxel or nitric oxide, efficiently induced tumor cell death. These results suggest that AGP has the potential to be a novel DDS carrier for anticancer agents.
纳米尺寸的血浆蛋白可以被用作仿生药物传递系统（DDS）来治疗癌症，因为这些血浆蛋白可以作为癌细胞的营养来源，同时基于载有抗癌药物的事实。这促使我们研究 α-酸性糖蛋白（AGP）在这方面的潜力，因为它是一种纳米尺寸的血浆蛋白，并且可以结合多种抗癌药物。药代动力学分析表明，AGP 在肿瘤组织中的分布比已经被确立为癌症 DDS 载体的人血清白蛋白更广泛。AGP 可能通过内吞作用途径被纳入肿瘤细胞。此外，根据 AGP 的一级结构推断，一种具有高形成α-螺旋能力的合成 AGP 衍生肽也被肿瘤细胞摄取。载有抗癌药物（如紫杉醇或一氧化氮）的 AGP 可有效诱导肿瘤细胞死亡。这些结果表明，AGP 有可能成为新型的抗癌药物 DDS 载体。
