Engineering of Neutrophil Membrane Camouflaging Nanoparticles Realizes Targeted Drug Delivery for Amplified Antitumor Therapy

Abstract

Jingshuai Wang,1,* Xuemin Gu,1,* Yiqin Ouyang,1 Lei Chu,1 Mengjiao Xu,1 Kun Wang,2 Xiaowen Tong1 1Obstetrics and Gynecology Department, Tongji Hospital of Tongji University, Shanghai, People’s Republic of China; 2Cancer Center, Shanghai East Hospital of Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun Wang Jimo Road 150, Pudong New District, Shanghai, People’s Republic of ChinaEmail [email protected] Tong Xincun Road 389, Putuo District, Shanghai, People’s Republic of ChinaEmail [email protected]: Although the neutrophil membrane (NM)-based nanoparticulate delivery system has exhibited rapid advances in tumor targeting stemmed from the inherited instinct, the antitumor effect requires further improvement due to inefficient cellular internalization in the absence of specific interactions between NM-coated nanoparticles and tumor cells.Methods: Herein, we fabricated drug-paclitaxel loaded NM camouflaging nanoparticles (TNM-PN) modified with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), favorable for the cellular internalization.Results: The results showed that TNM-PN exerted a significant cytotoxicity to tumor cells by TRAIL-mediated endocytosis and strong adhesion to inflamed endothelial cells in vitro. Due to TRAIL modification as well as the adhesive interactions between neutrophil and inflamed tumor vascular endothelial cells, tumors in TNM-PN group exhibited almost 2-fold higher fluorescence intensities than that of NM camouflaging nanoparticles and 3-fold higher than that of bare nanoparticles, respectively. Significant tumor inhibition and survival rates of mice were achieved in TNM-PN group as a consequence of prolonged blood circulations to 48 h and preferential tumor accumulations, which was ascribed to targeting adhesion originated from NM to immune evasion and subsequent excellent cellular internalization.Conclusion: The research unveiled a novel strategy of amplifying cellular internalization based on NM coating nanotechnology to boost antitumor efficacy.Keywords: neutrophil membrane camouflaging, nanoparticulate delivery, tumor targeting, cellular internalization, antitumor therapy

Keywords

• neutrophil membrane camouflaging
• nanoparticulate delivery
• tumor targeting
• cellular internalization
• antitumor therapy