AI Insight
Researchers developed hybrid nanoparticles by merging synthetic liposomes with macrophage-derived extracellular vesicles to deliver doxorubicin (DOX) to glioblastoma (GBM) cells. The optimal formulation, H-F2-DOX, achieved a particle size of approximately 163 nm, an encapsulation efficiency of 76.5%, and demonstrated pH-sensitive drug release, with notably higher release at acidic pH (90.7% at pH 5.5) compared to physiological pH (64.9% at pH 7.4), which is relevant given the acidic tumor microenvironment. Cell viability assays confirmed strong cytotoxic effects against GBM cells, with H-F2-DOX showing superior potency under hypoxia-mimetic conditions.
Why it matters
Glioblastoma remains one of the most treatment-resistant brain cancers, and this hybrid nanoparticle approach could improve targeted drug delivery by combining the biocompatibility of natural extracellular vesicles with the engineering versatility of synthetic liposomes. If validated in more advanced preclinical models, this strategy could contribute to overcoming the blood-brain barrier and the hostile tumor microenvironment that limit current therapies.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Glioblastoma (GBM) presents significant therapeutic challenges due to its aggressive nature, complex microenvironment and the limitations of conventional drug delivery systems. In this study, hybrid nanoparticles were developed by combining synthetic liposomes with macrophage-derived extracellular vesicles (EVs) to harness the strengths of both platforms. Two distinct liposomal formulations, DPPC:Chol:DSPE-mPEG2000 (F1) and DPPC:DPPS:Chol:DSPE-mPEG2000 (F2), were used as the basis for the synthesis. EVs derived from J774 macrophages were integrated with F1 and F2 to create hybrid nanoparticles (H-F1 and H-F2). Doxorubicin (DOX) was encapsulated using a pH gradient and a remote loading procedure. The mean particle size of H-F1-DOX and H-F2-DOX was 158.2{+/-}1 nm and 162.8{+/-}9 nm, respectively. The polydispersity index (PDI) was 0.130{+/-}0.012 and 0.084{+/-}0.033, while the zeta potential values were -14.9{+/-}0.7 mV and -26.7{+/-}3.1 mV, respectively. H-F2-DOX exhibited the highest encapsulation efficiency (EE%), reaching 76.5{+/-}3.4%. The encapsulated hybrids remained stable up to one week, at +5{degrees}C. The release of DOX from H-F2-DOX in DMEM supplemented with 10% serum showed pH sensitivity, with total DOX release of 64.9{+/-}5.3% at pH 7.4 and 90.7{+/-}6.5% at pH 5.5. The cell viability assay demonstrated that all formulations exhibited strong cytotoxic effects against GBM cells under normoxic conditions, with H-F2-DOX showing the most potent effect under hypoxia-mimetic conditions.