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 contraction 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; for FITC-BSA, a concentration of 300 µg/mL 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/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.