Sialic acid-conjugate modified liposomes targeting neutrophils for improved tumour therapy
Cong Li, Qiujun Qiu, Min Liu, Xinrong Liu, Ling Hu, Xiang Luo, Chao-Yang Lai, Dan Zhao, Hongxia Zhang, Xin Gao, Yihui Deng, Yanzhi Song
Abstract
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.