Engineered Artificial Human Neutrophils Exhibit Mature Functional Performance

Abstract

Neutrophils, a key innate immune component, are powerful effector leukocytes for mediating opposing effects on tumor progression and ameliorating pathogen infections. However, their short lifespan and complex purification process have limited neutrophil clinical applications. Here we combined genetic engineering technology with a nanodrug system to construct artificial neutrophils that display functions similar to those of native neutrophils. K562 and HL60 human leukemia cells were engineered to express the human G protein-coupled receptor hM4Di. Compared to the parental cells, engineered hM4Di-K562 and hM4Di-HL60 cells exhibited excellent chemotaxis ability towards clozapine-N-oxide (CNO) and superior bacteria phagocytic behavior, resembling native neutrophils. The antibacterial ability of the hM4Di-K562 cells was further enhanced by loading them with the glycopeptide vancomycin via mesoporous silica nanoparticles (Nano@Van). Our proposed artificial cell engineering platform provides a new avenue to investigate the physiological properties of neutrophils.

Convergence of nanomedicine and neutrophils for drug delivery

“…Some studies have also explored the use of human pluripotent stem cells induced into neutrophils using stage-specific chemical stimulators [ 110 ]. Others have exploited myeloid cells to engineer artificial neutrophils with outstanding functional performance [ 119 ]. These innovative approaches provide a promising avenue for achieving improved scalability and reproducibility, offering the potential for off-the-shelf neutrophil-based systems.…”