College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
Biomater Sci. 2020 Apr 21;8(8):2189-2201. doi: 10.1039/c9bm01732a. Epub 2020 Feb 25.
Neutrophils are the most abundant white blood cells in humans. Many tumor-treatment methods that are related to tissue infiltration and the activation of neutrophils have been developed. In particular, one strategy, which aims to improve tumor treatment, involves the exploitation or targeting of activated neutrophils. Peripheral blood neutrophils (PBNs) from tumor-bearing mice display high expression of l-selectin, which is well known to be targeted by the sialic acid (SA) ligand. Hence, in this research, we developed a drug delivery platform involving liposomes modified with an SA conjugate that targets activated PBNs. The uptake of doxorubicin (DOX)-loaded liposomes by PBNs did not alter their activation and transmigration. Furthermore, in tumor-bearing mice, SA-modified liposomes displayed a greater tumor-targeting ability and stronger tumor treatment efficacy, which were mediated by the neutrophil infiltration induced by inflammatory factors released from the tumor microenvironment. In conclusion, SA-modified liposomal DOX was shown to be an effective neutrophil-mediated drug delivery system for tumor therapy.
中性粒细胞是人类血液中最丰富的白细胞。已经开发出许多与组织浸润和中性粒细胞激活相关的肿瘤治疗方法。特别是,一种旨在改善肿瘤治疗的策略涉及利用或靶向激活的中性粒细胞。荷瘤小鼠的外周血中性粒细胞 (PBN) 高表达 L-选择素,众所周知,L-选择素是唾液酸 (SA) 配体的靶点。因此,在这项研究中,我们开发了一种涉及脂质体的药物递送平台,该脂质体用靶向激活的 PBN 的 SA 缀合物进行了修饰。阿霉素 (DOX) 负载的脂质体被 PBN 摄取不会改变其激活和迁移。此外,在荷瘤小鼠中,SA 修饰的脂质体显示出更强的肿瘤靶向能力和更强的肿瘤治疗效果,这是由肿瘤微环境中释放的炎症因子诱导的中性粒细胞浸润介导的。总之,SA 修饰的 DOX 脂质体被证明是一种有效的中性粒细胞介导的药物递送系统,可用于肿瘤治疗。