Engineering of Neutrophil Membrane Camouflaging Nanoparticles Realizes Targeted Drug Delivery for Amplified Antitumor Therapy
0301 basic medicine
Medicine (General)
Paclitaxel
Neutrophils
nanoparticulate delivery
TNF-Related Apoptosis-Inducing Ligand
Mice
03 medical and health sciences
R5-920
Drug Delivery Systems
International Journal of Nanomedicine
Albumins
Cell Line, Tumor
Neoplasms
Animals
Humans
Nanotechnology
Tissue Distribution
Original Research
Immune Evasion
Inflammation
0303 health sciences
Cell Death
tumor targeting
Cell Membrane
Endothelial Cells
Endocytosis
3. Good health
neutrophil membrane camouflaging
RAW 264.7 Cells
Nanoparticles
cellular internalization
antitumor therapy
DOI:
10.2147/ijn.s288636
Publication Date:
2021-02-14T21:30:49Z
AUTHORS (7)
ABSTRACT
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.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.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.The research unveiled a novel strategy of amplifying cellular internalization based on NM coating nanotechnology to boost antitumor efficacy.
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