Exploring paclitaxel–albumin-loaded neutrophil-like cells via microfluidic-based mechanical deformation for enhanced cargo delivery in glioblastoma therapy

Abstract

This study investigated the rapid drug delivery capabilities of neutrophil-like cells using a microfluidic chip-based mechanical deformation approach, with an emphasis on glioblastoma treatment at the cellular level. We designed a microfluidic chip comprising multiple constriction gaps and parallel microchannels to enable efficient drug loading into HL-60 cells and neutrophil-like cells derived from differentiated HL-60 cells (dHL-60 cells). Optimization was performed using dye molecules, including FITC–dextran (4 kDa, 20 kDa) and FITC–BSA, with delivery efficiency and the cell recovery rate serving as critical evaluation parameters. The optimal performance was achieved at a gap size of 8 μm and a flow rate of 150 μL min⁻¹; for FITC–BSA, a concentration of 300 μg mL⁻¹ was deemed suitable. Under these conditions, neutrophil-like cells loaded with albumin-bound paclitaxel (PTX–ALB) were successfully and rapidly prepared, yielding a delivery efficiency of 55.93 ± 19.7% and a drug loading of 784.20 ± 74.6 ng per 10⁵ cells, with a throughput of up to ∼10⁷ cells per hour. The chemotactic performance of PTX–ALB-loaded neutrophil-like cells did not change significantly, and these cells could cross the endothelial barrier constructed in vitro and exerted antitumour effects on U87-eGFP cells. The antitumour effects could be further strengthened by increasing the dosage of drug-loaded cells (from 4× 10⁵ cells to 1× 10⁶ cells) and extending the treatment duration (from 48 hours to 72 hours), which reduced U87-eGFP cell viability to 80 ± 7% and 62 ± 3%, respectively. This microfluidic-based mechanically mediated cargo delivery platform represents a rapid, high-throughput strategy for cell-based drug loading, with broad potential in cellular therapy and immunotherapy.