Department of Neurology and Stroke Center, The First Affiliated Hospital, Department of Chemistry, Jinan University, Guangzhou, 510632, China.
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Nanobiotechnology. 2022 Sep 5;20(1):401. doi: 10.1186/s12951-022-01593-5.
Cancer cell membrane-camouflaged nanotechnology for metal complex can enhance its biocompatibility and extend the effective circulation time in body. The ruthenium polypyridyl complex (RuPOP) has extensive antitumor activity, but it still has disadvantages such as poor biocompatibility, lack of targeting, and being easily metabolized by the organism. Cancer cell membranes retain a large number of surface antigens and tumor adhesion molecules CD47, which can be used to camouflage the metal complex and give it tumor homing ability and high biocompatibility.
Therefore, this study provides an electrostatic adsorption method, which uses the electrostatic interaction of positive and negative charges between RuPOP and cell membranes to construct a cancer cell membrane-camouflaged nano-platform (RuPOP@CM). Interestingly, RuPOP@CM maintains the expression of surface antigens and tumor adhesion molecules, which can inhibit the phagocytosis of macrophage, reduce the clearance rate of RuPOP, and increase effective circulation time, thus enhancing the accumulation in tumor sites. Besides, RuPOP@CM can enhance the activity of cellular immune response and promote the production of inflammatory cytokines including TNF-α, IL-12 and IL-6, which is of great significance in treatment of tumor. On the other hand, RuPOP@MCM can produce intracellular ROS overproduction, thereby accelerating the apoptosis and cell cycle arrest of tumor cells to play an excellent antitumor effect in vitro and in vivo.
In brief, engineering cancer cell membrane-camouflaged metal complex is a potential strategy to improve its biocompatibility, biological safety and antitumor effects.
癌细胞膜伪装纳米技术可用于金属配合物,以提高其生物相容性并延长其在体内的有效循环时间。钌多吡啶配合物(RuPOP)具有广泛的抗肿瘤活性,但仍存在生物相容性差、缺乏靶向性、容易被机体代谢等缺点。癌细胞膜保留了大量的表面抗原和肿瘤黏附分子 CD47,可用于伪装金属配合物,赋予其肿瘤归巢能力和高生物相容性。
因此,本研究提供了一种静电吸附方法,利用 RuPOP 与细胞膜之间正负电荷的静电相互作用构建了一种癌细胞膜伪装的纳米平台(RuPOP@CM)。有趣的是,RuPOP@CM 保持了表面抗原和肿瘤黏附分子的表达,能够抑制巨噬细胞的吞噬作用,降低 RuPOP 的清除率,延长有效循环时间,从而增强在肿瘤部位的积累。此外,RuPOP@CM 能够增强细胞免疫反应的活性,促进 TNF-α、IL-12 和 IL-6 等炎症细胞因子的产生,这在肿瘤治疗中具有重要意义。另一方面,RuPOP@MCM 可以产生细胞内 ROS 过度产生,从而加速肿瘤细胞的凋亡和细胞周期停滞,在体外和体内发挥优异的抗肿瘤作用。
总之,工程化的癌细胞膜伪装金属配合物是提高其生物相容性、生物安全性和抗肿瘤效果的一种有潜力的策略。