Evaluation of nanoparticle albumin-bound paclitaxel loaded macrophages for glioblastoma treatment based on a microfluidic chip

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (M phi) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/M phi. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/M phi.Methods: In this study, we constructed nab-PTX/M phi by incubating live M phi with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/M phi, we treated the GBM-on-a-chip model with nab-PTX/M phi and investigated GBM cell proliferation, migration, and spheroid formation.Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of M phi. The uptake of nab-PTX by M phi occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/M phi exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, M phi were able to release nab-PTX, and the release of nab-PTX by M phi had nearly reached its limit at 48 h. Compared with control group and blank M phi group, individual nab-PTX group and nab-PTX/M phi group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/M phi was more significant than nab-PTX.Discussion: Our findings demonstrate that nab-PTX/M phi has a significant anti-GBM effect compared to individual nab-PTX or M phi administration, suggesting M phi as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.